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Thomas Risler
On larger length scales, the appearance of coordinated made of a collection of hundreds of identical protein sub-
motion in large collections of proteins relies on collective units called flagellins [18]. The swimming of a single
phenomena, self-organization and dynamical symmetry bacterium can be impressively rapid, as bacteria such
breakings [13]. On yet larger length scales, swimming of as Escherichia coli - the common intestinal bacterium
microorganisms has attracted the attention of physicists - swim at speeds of 20 to 30 micrometers per second,
for years [14, 15], and morphogenesis and pattern for- for the cell itself is only about two-micrometer long and
mations in cellular tissues rely on self-organization phe- half a micrometer in diameter. The bacterium possesses
nomena, as was envisioned for the first time by Turing in multiple flagella that gather together during swimming,
1952 [16, 17]. Therefore, in addition to biophysical ex- and can fly apart as the bacterium switches direction.
perimental techniques, variety of theoretical physics’ dis- Other bacteria such as Vibrio cholerae - the causative
ciplines spanning the theory of stochastic processes, sta- agent of cholera - use a single flagellum located at one of
tistical physics, out-of-equilibrium thermodynamics, hy- their pole, but the propulsion mechanism relies always on
drodynamics, nonlinear dynamics and pattern formation the presence of a rotary molecular motor located in the
have contributed and still contribute to our understand- cell membrane, and which is sensitive to modifications
ing of cell motility. of the chemical environment of the cell. Under normal
The present article will mainly focus on the eukary- conditions, the bacterium changes direction in an inter-
otic cytoskeleton and cell-motility mechanisms. Bacterial mittent chaotic way by reversing the rotational direction
motility as well as the composition of the prokaryotic cy- of its motors, a phenomenon known as tumbling. When
toskeleton will be only briefly mentioned. The article is placed in a concentration gradient of nutrients however,
organized as follows. In Section III, we will first present the cell can adapt its tumbling frequency to swim towards
an overview of the diversity of cellular motility mech- nutrient-rich regions, a phenomenon known as chemo-
anisms, which might at first glance be categorized into taxis [19].
two different types of behaviors, namely “swimming” and Even though it shares the same name, the eukaryotic
“crawling”. Intracellular transport, mitosis - or cell divi- flagellum shares little structures and propulsion mecha-
sion - as well as other extensions of cell motility that rely nisms with its bacterial counterpart. It is indeed at least
on the same essential machinery will be briefly sketched. ten times larger than a bacterial flagellum in both di-
In Section IV, we will introduce the molecular machin- ameter and length, and instead of being a rigid passive
ery that underlies cell motility - the cytoskeleton - as well structure animated by a remote motor, it bears its mo-
as its interactions with the external environment of the tor activity along its length. Propulsion occurs by the
cell and its main regulatory pathways. Sections IV D to propagation of a bending wave along the flagellum as a
IV F are more detailed in their biochemical presentations; result of the relative sliding of a group of about 10 long
readers primarily interested in the theoretical modeling parallel filaments, which are engulfed in the cell’s plasma
of cell motility might want to skip these sections in a first membrane and are animated by hundreds of motor pro-
reading. We will then describe the motility mechanisms teins in a coordinated manner. Eukaryotic cells also use
that rely essentially on polymerization-depolymerization another type of protrusions to swim, the cilia, which are
dynamics of cytoskeleton filaments in Section V, and the much like flagella in their internal structure, but which
ones that rely essentially on the activity of motor pro- are shorter and work usually in numbers, covering some-
teins in Section VI. Finally, Section VII will be devoted times the whole cell surface as in the case of paramecia
to the description of the integrated approaches that have or other ciliated protozoa (see Fig. 1). Their beating
been developed recently to try to understand the coop- pattern is then coordinated at the cellular level, most of-
erative phenomena that underly self-organization of the ten in a wave-type of manner known as the metachronal
cell cytoskeleton as a whole. wave. Beating cilia are also found in animals, as for ex-
ample in humans where ciliated cells play major roles in
several organs like the brain, the retina, the respiratory
III. THE DIVERSITY OF CELL MOTILITY tract, the Fallopian tube and the kidney [20].
Other strategies of swimming include the elegant
A. Swimming movement used by Eutreptiella - called metaboly - which
consists in gradually changing the contour of the cell sur-
At the cellular level, viscous hydrodynamic forces are face to locally increase the drag exerted by the viscous
several orders of magnitude higher than inertial forces. fluid around and move the cell forward [21]. Other organ-
Therefore, simple reciprocal motions cannot produce for- isms like most motile species of Chrysophytes - a group
ward motion, and cellular swimming patterns need to be of marine photosynthetic protozoa - possess a flagellum
asymmetric in space and time for the cell to advance. attached at their front instead of their back. The flag-
This hydrodynamic problem faced by cells attempting to ellum is covered with stiff hairs projecting from its side
swim have been eloquently summarized by Purcell as “life that allow the cell to move forward as a planar wave
at low Reynolds number” [15]. To solve this problem, propagates from the base to the tip of the flagellum [2].
bacteria use the rotation of a short helical or corckscrew- Finally, one should mention yet another type of motility
shaped flagellum, which is a relatively rigid structure - namely walking - in which cells use also cilia and flag-
5
ella animated in a coordinated manner to enable the cell direction [23, 24] (see Fig. 4). To these must be added
to literally “walk” over surfaces. Walking motility relies
on the same essential biochemical structures as the ones
employed in swimming with collections of cilia.
B. Crawling
FIG. 8: (a) ATP-hydrolysis cycle, with the respective du- FIG. 9: Schematic representation of muscle myofibrils, the
rations τon and τoff of the attached and detached states basic contractile fibers of skeletal muscles. Actin and myosin
of the motor. These durations define the duty ratio r as filaments are periodically arranged in a polarity-alternated
r = τon /(τon + τoff ). (b) During the attached phase, the head fashion. Between two “Z discs” is found the elementary struc-
of the motor makes a working stroke of working distance δ. ture that is periodically repeated, the sarcomere, and where
The motor then unbinds from the filament, and makes a re- relative sliding of actin and myosin filaments leads to contrac-
covery stroke during the detached phase. By recovering its tion. Source: courtesy of Karsten Kruse.
initial conformation while detached, the motor avoids step-
ping backwards and so progresses by a distance equal to the
working stroke during each cycle. Source: reprinted from ref.
[56] with permission from Nature Publishing Group. myosins, but diverge in their tail structures [58]. They
walk on microtubules instead of actin filaments, are pro-
cessive, and are involved mainly in intracellular transport
proteins can be divided into a motor domain, called the like the transport of organelles along nerve axons[309].
head, and a tail or base. The head is the site of conforma- The kinesin superfamily has been divided into 14 fami-
tional change of the protein during ATP-hydrolysis, and lies, and a number of “orphans” that are so far ungrouped
with which the motor attaches to the filament. The tail [59]. Most kinesin motors are plus-ended directed, like
connects the motor to its cargo or to other motors. Pro- the conventional kinesin I that founded the family [60].
cessive motors are (homo-)dimers, such that as one head Members of the Kinesin-13 family are unconventional,
is attached to the filament, the other can move to a new in that they can processively induce microtubule depoly-
binding site. In that case, the two tails of the associated merization, a process that is essential to chromosome seg-
monomers wind up together to hold to each other. Non- regation during mitosis[310] [61] (see next Section).
processive motors can also be found in dimeric forms, one Dynein proteins are less well-characterized. It is also
of the two heads being then just unused. unknown whether they share a common ancestor with
myosins and kinesins, or whether they are the result of
convergent evolution. Two major groups of dyneins ex-
C. Motor families ist: axonemal dyneins, which drive the bending of eu-
karyotic cilia and flagella by inducing the relative sliding
Eukaryotic cytoskeletal motor proteins are divided of microtubules [62], and cytoplasmic dyneins, which are
into three superfamilies, namely myosins, kinesins and involved in organelle and vesicular transport, as well as
dyneins. The motor proteins known longest belong to cell division [63]. Most dyneins are minus-ended directed,
the myosin superfamily [57], because of their high con- and interestingly, some dyneins can be non-processive at
centration in skeletal muscles. All myosin motors walk on high, but processive at low ATP concentrations.
actin filaments through a general four-step process: bind-
ing, power-stroke, unbinding, and recovery-stroke[307]
[56] (see Fig. 8). Today, they are classified into 18 dif- D. Other cytoskeleton-associated proteins
ferent classes, with possibly dozens of different members
in each class, even in a single organism. The skeletal- The coordination of the numerous different processes
muscle myosins belong to the Myosin II family; they that happen during amoeboid motility rely on a tight reg-
have long tails that form dimeric α-helices and associate ulation of the activity of the cell cytoskeleton, as well as
into the so-called “thick filaments” originally observed its anchoring to the substrate. In particular, as we shall
by H. E. Huxley and J. Hanson, while the “thin fila- see below, the protrusion of the leading edge of the cell
ments” are F-actin polymers [3–5] (see Fig. 2 and 9). - the first step of amoeboid motility - relies on the for-
Most myosin molecules are plus-ended directed (to the mation of a highly-cross-linked and dynamic network of
exception of Myosin VI), and non-processive (to the ex- actin filaments. Its formation and dynamical regulation
ception of Myosin V, which is involve in vesicular trans- are carried out with the help of numerous accessory pro-
port). Their very diverse mechanical features, in terms teins [23, 64]. Following Pollard’s presentation [65, 66]
of step sizes, duty ratios and stepping speeds, are very (see Fig. 10), we can focus on the main proteins that
fine-tuned to their functions[308] [56]. are involved in the formation, structure and dynamics of
Kinesin proteins share very similar structural features the actin network. Nucleation of the network starts after
with myosins in their head domain and are therefore biochemical signals have been integrated via G-protein-
thought to have branched from a common ancestor with linked membrane receptors, namely small GTPases and
10
D
∂t P (x) = D ∂x2 P (x) + f ∂x P (x) + kon P (x + δ) − koff P (x) for x < δ,
kB T
D
∂t P (x) = D ∂x2 P (x) + f ∂x P (x) + kon [P (x + δ) − P (x)] − koff [P (x) − P (x − δ)] for x > δ, (2)
kB T
where notations are similar to the ones used in Eq. (1), bending fluctuations of the growing filament, this led to
and to which must be added the effective diffusion co- the Elastic Brownian Ratchet Model [151], a generaliza-
efficient D for the distances x between the filament and tion of which is the Tethered Elastic Brownian Ratchet
the membrane. The time-dependence of P is implicit. Model [152] that considers that some filaments are at-
Using vanishing-current conditions at the leading edge tached to the membrane via protein complexes (as it
x = 0, the stall force can be obtained and is given by an has been observed in the Listeria-propulsion mechanism
expression analog to that of microtubules models, with for example) and therefore do not exert polymerization
a1 = δ being the size of a G-actin monomer. Including forces. When typical parameter values are plugged into
15
these models, single actin-filament force generation is es- namely molecular and mesoscopic, continuum models.
timated to be of the order of 5-7 pN [153]. Taken into We have already reviewed the molecular models that rely
account that at the leading edge several hundreds of actin on brownian-ratchet mechanisms. They, in particular,
filaments per micron work together to drive the cell for- have led to force-velocity curves that are consistent with
ward, the resulting force is of the order of nanonewtons some observations of Listeria motion [152, 158]. Contin-
per micron [152], a force large enough to tackle the mem- uum models describe the actin network as a compress-
brane load and resistance. However, it has since then ible elastic gel with an elastic modulus of about 5000 Pa
been claimed that motor proteins, called end-tracking [136, 163, 164] (see also Section VII C). When growing
motors, should be required to explain observed forces in over a curved surface like the bacterium Listeria or a
the case of Listeria propulsion for example [154]. This coated bead, the gel deforms as it grows by monomer
work has been reviewed in [41]. additions on the particle surface, which in turn gener-
Lateral interactions between filaments in an actin net- ates a stress that pushes the particle forward [163, 164].
work have been investigated via models that take into ac- Monomer transport to the inner surface of the growing
count the branching structure of the network [155, 156]. gel is purely diffusive, with a diffusion constant that has
In particular, Autocatalytic Models assume that new been estimated to be of the order of 2 µm2 /s for actin
branches are generated from existing ones, which leads monomers in an ActA-produced gel [165]. When origi-
to a growth velocity that is independent of the load nally initiated on a spherical object like a rigid bead, the
[156]. To investigate the consequences of these mod- growth of the gel layer starts isotropic, but ruptures into
els, two approaches have been followed, namely stochas- a comet-type growth because of mechanical instability.
tic simulations of the growing actin network, tracking The instability relies on a positive feedback that involves
each filament position and orientation [155], and deter- creation of a tensile stress as the gel grows because of
ministic rate equations that include growth, capping and geometrical effects, and enhancement of the depolymer-
branching rates, and which led to a comparison between ization rate or rupture of the gel in regions of enhanced
ratchet and autocalytic models [156]. Experimental tests tensile stress [166]. The instability occurs less rapidly
of the two models have been performed in in-vitro sys- with increasing bead size, which explains why movement
tems, using Listeria propulsion as well biomimetic sys- is more often observed with small beads. This mecha-
tems [157] (see next paragraph). While some Listeria nism of tensile-stress accumulation and rupture can also
studies favored the Tethered Elastic Brownian Ratchet explain the saltatory motion observed with Listeria mu-
Model [158], some studies using biomimetic systems fa- tants and coated beads in some conditions [162]: rapid
vored the Autocatalytic Model [159], and several others phases of motion are due to the sudden rupture of the
neither of them. A possible explanation for these appar- gel that pushes the particle forward, as slow phases of
ently contradictory results may be that different exper- motion correspond to progressive build-up of lateral ten-
imental studies led to analyzing different regimes of the sile stress. Depending on the size of the bead as well as
force-velocity curve. the concentration of proteins at its surface, this dynamic
instability can be present or not, which explains the ob-
servation of both continuous and saltatory regimes with
D. A model system for studying actin-based coated beads as well as Listeria bacteria [162, 167].
motility: The bacterium Listeria monocytogenes To further explore the properties of the actin gel and
the Listeria-propulsion mechanism, experiments with
As earlier stated, our understanding of eukaryotic soft objects like liposomes [168, 169], endosomes [170]
actin-based motility has grandly benefited from the and oil droplets [171] have been performed. They show
motility mechanism of the bacterium Listeria monocy- that the actin gel squeezes the object, compressing its
togenes (see Section V B). While velocities of Liste- sides and pulling its rear, an effect that gives it a pear-
ria bacteria in a homogeneous environment are typically like shape (see Fig. 14). Analysis of the contour of the
constant, some mutants progress in a saltatory manner deformed objects provides informations on the distribu-
[160]. This observation has been later reproduced in in tion of the normal stress on the surface of the object.
vitro motility assays using latex beads coated with the This could in principle allow for the derivation of the
bacterium transmembrane protein ActA (that further total force exerted on the load in the case for example
recruits Arp2/3) [161], or directly with VCA proteins, of oil droplets, where interfacial tension is measurable
a sub-domain of WASP that is responsible for actin- and normal stress can be deduced from Laplace’s law
branching and polymerization nucleation [162]. Such [171]. But in fact, assuming a constant surface tension,
biomimetic systems have allowed for the direct measure- the integration of the normal stress over the surface of the
ment of the characteristic polymerization force that is droplet gives a zero net value of the force that is indepen-
produced by an actin gel [136], and for the overall study dent of the droplet shape, the latest being regulated by
of actin-based motility mechanisms in simple and well- the variation of the polymerization velocity with normal
controlled conditions [40, 41, 157]. stress. Instead, the distribution of actin-polymerization
Theoretical understanding of such actin-based propul- promoters on the surface of the droplet follows the gel
sion mechanisms has come from two different angles, elastic deformations, which in turn creates pressure vari-
16
the stress tensor is then obtained as σαβ = λuγγ δαβ + at different temperatures) can rectify the brownian
2µuαβ , where λ and µ are the Lamé coefficients, which motion of a given particle and lead to its directed motion
further leads to a position-dependent tensile stress as was [189]. For motor proteins, as we have already discussed,
introduced phenomenologically in [181]. While traveling temperature inhomogoneities in the system cannot
through the lamellipodium, tangential stress builds up, hold long enough to ground the mechanism. Instead,
which leads to rupture of the adhesion points once a crit- various different isothermal rectifying models have
ical force has been passed, and eventually drags the cell been discussed to describe the underlying mechanisms
body forward. Therefore, within this framework, only of different biophysical processes [11, 190]. Among
one parameter is directly controlled by the pH - namely these, one can mention the translocation of proteins
Λ - and the pH in particular does not need to influence and force-generation by linear molecular motors (which
directly adhesion strength. includes cytoskeletal motors, but also motors acting on
DNA or RNA, like DNA-polymerases, RNA-polymerases
and helicases), the ion transport in ion pumps, and the
VI. MOTOR-DRIVEN MOTILITY rotary-motor processes such as the one found in the
F0F1-ATPase or the bacterial flagellar motor. Such
A. Generic considerations isothermal rectifying processes and their underlying
physical principles have been extensively reviewed in
[12, 13]. They all rely on a Langevin type of description
Despite the major role played by polymerization forces
of an overdamped particle of position x, moving in
in cellular motility, and in particular as we have previ-
a spatially-periodic potential W (x) that reflects the
ously seen in amoeboid motility, a vast amount of di-
motor-filament interaction, and subjected to a viscous
verse motile processes in eukaryotic cells is driven by
friction with coefficient ξ and a fluctuating force f (t)
motor proteins (see Section IV B). Theoretical studies
that reflects the stochasticity of thermal fluctuations:
of molecular motors started with the cross-bridge model
published independently by A. F. Huxley and H. E. Hux-
ley to explain the relative sliding of myosin filaments with dx
respect to actin filaments in cross-striated muscle fibers ξ = −∂x W (x) + f (t). (4)
dt
[8, 184]. This approach was later formalized by Hill [185],
who introduced the notion of different “states” of a motor To rectify brownian motion, three different approaches
protein, each of these corresponding to a thermodynamic- have been mainly followed, namely (i) random forces
equilibrium state. Interpretation of these different states f (t) whose fluctuations do not satisfy the fluctuation-
was given in terms of different conformations of the mo- dissipation (FD) relation, (ii) fluctuating potentials
tor protein and its interaction with the filament, or in W (x, t) that are time-dependent, and (iii) particle fluc-
terms of the state of the hydrolysis reaction of ATP, tuating between states, where different states indexed by
or both [55, 186]. Justification for considering differ- i = 1, ..., N reflects different conformations of the protein
ent thermodynamic-equilibrium states relied on the ob- and interactions with the filament.
servation that for the transient response of muscles, the In the following, no attempt will be made to exten-
fastest response was known to be in the range of millisec- sively present the literature on molecular motors. We
onds, as thermal equilibrium on molecular characteristic shall instead only briefly sketch the generic consider-
length scales of 10 nm occurs after at most a few hun- ations of the main proposed models, and focus more
dreds of nanoseconds. In this class of models, progres- closely on a particular example of them, the two-state
sion of the motor along the filament relies on asymmet- model, which has allowed for an understanding of the
ric transition rates of the particle between the different appearance of spontaneous oscillations in systems of cou-
states, for which asymmetry of the filament and energy pled motors. This generic mechanism has been proposed
consumption by the motor is required. Typically, after to underly axonemal beating, the generic mechanism that
one cycle of conformational states, the motor protein has powers eukaryotic flagellar and ciliary-based motilities.
progressed by one or several allowed binding sites on the
periodic lattice represented by the cytoskeletal filament.
In between, up to five or six different states could be in- B. Phenomenological description close to
volved [185, 187]. Experimental confirmation came later thermodynamic equilibrium
with the direct observation of walking steps displayed
by advancing molecular motors [53]. Such observations Sufficiently close to thermal equilibrium, out-of-
were first obtained studying kinesin motors in in-vitro equilibrium perturbations can be described using a
motility assays, and later with myosin motors displacing generic linear-response theory that introduces general-
a filament that was attached to two glass beads placed ized forces which drive generalized currents [191]. In the
in laser-trap potentials [188]. For a review, see [54]. context of molecular motors, the generalized forces that
Another class of models relies on the generalization drive the system out of equilibrium are the mechanical
of Feynman’s famous “thermal ratchet”, in which the force fext acting on the motor (including drag), and the
presence of different heat baths (namely thermal baths chemical-potential difference ∆µ of the chemical reac-
18
tion ATP
ADP+Pi that drives motor power [13, 192]. models that are used to study various transport phe-
Linear-response theory then gives: nomena, like ionic transport in solids or traffic flow with
bulk on-off ramps [195]. In the simplest case of the ab-
v = λ11 fext + λ12 ∆µ, sence of particle attachment and detachment, the model
r = λ21 fext + λ22 ∆µ, (5) reduces to the Asymmetric Simple Exclusion Process
(ASEP) [196], originally introduced to describe the trans-
where the coefficients λij are phenomenological response lation of messenger RNA by ribosomes [197]. Including
coefficients. Here λ11 and λ22 can be viewed respectively attachment-detachment rates, the next simplest case de-
as a standard and generalized mobilities, and λ12 and scribes the space surrounding the filament as a reser-
λ21 as mechano-chemical couplings. Onsager relations voir of uniformly-distributed particles [198, 199]. A sec-
impose that λ12 = λ21 , and the Second Law of Ther- ond possibility is to include the dynamics of unbound
modynamics insures that the dissipation rate is positive: particles explicitly, for example on a cubic lattice [200].
T Ṡ = fext v + r∆µ ≥ 0. Whenever both of the two terms Boundary terms can also play an important role, and dif-
that appear in this inequality are positive, the system is ferent possible choices have been considered depending
passive, but it works as a motor when fext v < 0, and as on the biological situation [201].
generator of chemical energy when r∆µ < 0. The lat- Consequences of these models are illustrated by vari-
ter function is not known for linear motors, but is the ous important phenomena. Among these, one can find
common mode of operation of F0F1-ATPase, the protein the followings: anomalous transport due to repeated at-
complex that synthetizes ATP from electro-chemical en- tachments and detachments [200, 202, 203], domain walls
ergy that is stored in proton gradients [1, 52] (see Sec- that separate regions of high and low motor densities in
tion IV B). The reversibility of this rotary engine can the filament [199, 200], phase separation in systems with
be related to the predicted reversibility that comes out two motor species [204], and phase transitions when co-
of linear-response theory: in the absence of an exter- operative binding-unbinding is introduced [205]. For a
nal force, reversing the chemical potential difference ∆µ recent review on these collective traffic phenomena, see
should reverse the sign of the velocity v without a need [206] and references therein.
for a change in the mechanism.
D. The two-state model
C. Hopping and transport models
One model that proved to be particularly useful for
Within the first class of models that we have men- describing the rectification of brownian motion via cou-
tioned earlier, namely hopping models between different pling to chemical hydrolysis reactions, is the so-called
discrete equilibrium states of the motor-filament system, “two-state model”. In this description, the molecular
generic transition rates and periodicity in theses tran- motor switches stochastically between two different in-
sition rates, related to periodicity of the filament, are teraction states with the filament, that are described by
generally assumed. Within this framework, one can cal- two different asymmetric and l-periodic potentials W1
culate the mean velocity v and the diffusion coefficient D and W2 representing polarity and periodicity of the fila-
of the molecular motor from analyzing the generic associ- ment [13, 192, 207–212] (see Fig. 15a). The dynamics of
ated Master Equation [193]. For non-zero mean velocity this system can be conveniently represented in terms of
to occur, at least one of the transitions between states two coupled Fokker-Planck equations that describe the
must break detailed balance, a feature that can be associ- evolution of the probability density Pi (x, t) of the motor
ated with chemical energy consumption. In the simplest to be in state i = 1, 2 at position x at time t. Explicitly,
case of only two possible states of the motor protein, one we have:
can derive simple compact expressions for v and D [194]. ∂t P1 + ∂x J1 = −ω1 P1 + ω2 P2 ,
Their dependence on the external force further leads to
the derivation of the force-velocity curve, as well as a ∂t P2 + ∂x J2 = ω1 P1 − ω2 P2 . (6)
simple expression for the stall force, namely the force at
The currents Ji (i = 1, 2) result from diffusion, interac-
which the motor protein ceases to progress on average.
tion with the potentials Wi , and the external force fext :
To describe protein trafficking on a filament where
many motors are simultaneously engaged, like it is com- Ji = µi [−kB T ∂x Pi − Pi ∂x Wi + Pi fext ] . (7)
monly the case for example in organelle transport by ki-
nesin proteins along microtubules, one can reduce the The transition rates ωi (x) (i = 1, 2) between the two
number of states that a motor can occupy to one per states are driven out of equilibrium by ATP consumption,
filament binding site. Motors are then represented by whose strength can be represented by a single parameter
particles that move on a one-dimensional lattice with ho- Ω using the following form:
mogeneous transition rates, to which attachment and de-
tachment rates from and toward the bulk can be added. W1 (x) − W2 (x)
ω1 (x) = ω2 (x) exp + Ω Θ(x), (8)
This description belongs to a class of driven lattice-gas kB T
19
∂t P1 + v∂ξ P1 = −ω1 P1 + ω2 P2 ,
∂t P2 + v∂ξ P2 = ω1 P1 − ω2 P2 . (9)
self-organization of the dynein motors. This collective ulations [232–234], and analytical descriptions that can
behavior has been proposed to explain the bending waves be roughly divided into three categories, namely micro-
of cilia and flagella [214, 223] and analyzed in the frame- scopic, mesoscopic, and macroscopic or phenomenologi-
work of the two-state model [224, 225]. Close to the oscil- cal hydrodynamic descriptions. The first analytical ap-
latory instability, wave-patterns can be computed, whose proaches that have been developed correspond to meso-
frequencies and shapes depend on the filament length and scopic descriptions. There, starting from a microscopic
boundary conditions, and which are in good agreement description of the filaments, the effect of active cross-
with observed flagellar beating patterns [226]. linkers is described via motor-induced relative velocities
In the case of cilia however, beating patterns are typi- of paired filaments, where the form of such velocities
cally assymetric, like it is at best exemplified in the case is inferred from general symmetry considerations [235–
of the two cilia of the green alga Chlamydomonas [2], an 239]. Microscopic approaches start from what is known
observation that cannot be accounted for by investigat- about the properties of the different molecular players
ing beating patterns at the oscillatory instability only. involved and their interactions, and aim to build large-
Using the same underlying model, it has been proposed scaled coarse-grained theories from statistical physics’
that this assymetry originates from the presence of trans- principles [240–247]. Finally, macroscopic hydrodynamic
verse external flow that occurs as the organism is swim- approaches have adopted a more phenomenological point
ming [227]. In that case, the cilium tends to beat faster of view: they harness the generic symmetry and dynam-
and quite straight in the direction of the flow, whereas it ical properties of the players involved, to derive directly
comes back slower and more curved against it, a beating effective continuous theories in terms of a few coarse-
pattern that evokes power and recovery strokes. Hydro- grained fields [248–260]. Recently, attempts have been
dynamics has also been proposed to be responsible for made to bridge microscopic to macroscopic models, and
dynamic coupling of adjacent cilia, which results in both compare what results in being similar and different in the
spontaneous symmetry breaking and synchronization of two types of approaches [243, 245, 261].
their beating pattern [227]. This effect could be at the Interests for describing the cytoskeleton as an ensem-
basis of the observed beating waves that propagate for ble of filamentous polymers actively connected by cross-
example on the surface of paramecia[316] as they swim, linkers have come to the scene since self-organizations
which originate from a constant phase difference in the of motor-filament mixtures were observed experimen-
beating of the adjacent cilia, and which have been called tally [232, 233, 262]. Among these, complex patterns
metachronal waves [2, 227, 228]. This could also underly that include asters, vortices, spirals and connected poles
the breaking of symmetry that occurs in mammalian de- or networks have been observed in confined quasi-two-
velopment during gastrulation, and which is responsible dimensional systems in in vitro experiments [232, 233]
for left-right asymmetry. In that case, it has been shown (see Fig. 16). Patterns where shown to be selected in
that beating of cilia located in a transiently-formed ep- a way that is dependent on motor and ATP concentra-
ithelial chamber known as the node, create a directional tions, and numerical simulations based on microscopic
flow which transports signaling molecules preferentially models of rigid rods connected by active elements have
to one side [2, 20, 229]. There, beating patterns are un- shown to be capable of reproducing the experimental re-
usual in that cilia swirl in vortical fashion rather than sults [233]. Further experiments were performed on sys-
beat [230], and hydrodynamic-driven synchronization of tems that resemble more closely a living cell, and which,
these three-dimensional beating patterns has also been while being simplified versions of it, still exhibit some of
studied [231]. its behaviors. Along these lines, formations of bipolar
spindles that do not contain any microtubule-organizing
center were observed using cell extracts [263], and cell
VII. PUTTING IT TOGETHER: ACTIVE fragments that contain only the actin cortex where found
POLYMER SOLUTIONS to self-propagate on a substrate, with coexistence of lo-
comoting and stationary states [264, 265].
The last part of this review is devoted to the presen-
tation of some generic descriptions of the cell cytoskele-
ton, when considered as a network of long protein fila- A. Mesoscopic approaches
ments that are cross-linked by a variety of smaller pro-
teins. As already discussed, filamentous proteins that Theoretical modeling of the cell cytoskeleton have ben-
are involved in the cell-cytoskeleton dynamics are mostly efitted from the knowledge accumulated in equilibrium
F-actin and microtubules (made of G-actin and tubulin statistical physics of polymer solutions and liquid crystals
monomers), with which interact cross-linkers that can be [266]. However, the cell cytoskeleton is an active medium
either passive and stationary (such as α-actinin), or ac- for which new analysis techniques needed to be developed
tive and mobile, consisting then of clusters of molecular in order to describe, for example, its ability to actively
motors (mostly myosin and kinesin motors) (see Section self-organize, exert forces and create motion. First, the-
IV). To model these systems, different complementary oretical models have aimed to describe pattern forma-
approaches have been developed, namely computer sim- tions in systems of actively-driven rigid filaments in one-
21
B. Microscopic approaches
the interaction between filaments of the same orienta- ized thermodynamic forces and fluxes that are related to
tion has been shown to be important for contraction to each other by linear-response theory. Constraints on the
occur. Interestingly, the broken directional symmetry generic coupling constants to linear order emerge from
of the polarized state yields an effective drift velocity the spatio-temporal symmetries of the system, and cor-
that describes filament advection. This convective-type respond to the Onsager relations and the Curie princi-
term describes a genuine out-of-equilibrium contribution ple [191]. Inspired by the dynamics of liquid crystals
that is structurally not present in phenomenological de- [266, 281], a hydrodynamic theory has been developed
scriptions based on systematic linear expansions close to that describes the cytoskeleton as a visoelastic polar gel,
thermodynamic equilibrium (see below). Such a term driven out of equilibrium by a source of chemical energy
is reminiscent of the one introduced in earlier studies of [254–258] (this work has been reviewed in [259]). Among
self-propelled nematic particles [248, 251, 271], as well as other applications, such or similar approaches have been
of the explicit flow of the solvent taken into account in applied to the description of pattern formation in motor-
[254, 255, 257]. Other effects of higher-order nonlinear microtubule mixtures [250, 253], as well as the collective
terms have also been discussed in [272, 273], where pat- dynamics of self-propelled particles [248, 251, 252, 282].
tern selection between stripe patterns and periodic asters Originally, this hydrodynamic theory has been pre-
occurs via nonlinear interactions. sented as a generic theory for active viscoelastic materials
made of polar filaments, referred to as active polar gels
[255]. Within the framework of the previously-described
C. Macroscopic phenomenological approaches: The general formalism, here applied to the cytoskeleton, con-
active gels served quantities are the different number densities that
enter the dynamics, namely the number densities of sub-
units in the gel, of free monomers, and of respectively
The third category of approaches that have been de-
bound and unbound motors to the filaments. To these
veloped to try to understand the dynamical behavior of
must be added the solvent density and the total me-
the cell cytoskeleton as a whole, are effective phenomeno-
chanical momentum. Source terms in the conservation
logical theories which rely on the hypothesis that large
equations correspond to polymerization and depolymer-
length- and time-scales behaviors of the cytoskeleton are
ization of cytoskeleton filaments, attachment and detach-
largely independent of the microscopic details that un-
ment of motor proteins to the filaments, and the potential
derly its dynamics, but depend instead only on a few
presence of an external force. Order parameters corre-
macroscopic fields that capture the relevant behavior.
spond to orientational order parameters that originate
Sufficiently close to thermodynamic equilibrium, these
from the polarity of the filaments. Namely, they cor-
relevant fields describe the hydrodynamic modes (or slow
respond to momenta of the local polarization vector of
modes) of the dynamics, namely the modes whose relax-
individual filaments u, and most often only the first mo-
ation rates go to zero at long wavelengths. As for equilib-
mentum p = hui is considered that represents the locally-
rium systems close to a critical point, such hydrodynamic
averaged polarity in the gel[317]. To these must be added
modes correspond to the conserved densities on the one
a crucial parameter that drives the system out of equilib-
hand, and the order parameters that break continuous
rium, and which originates from the actively-maintained
symmetries on the other hand [191, 274]. To write generic
source of chemical energy in the cell, corresponding to
theories for the dynamics of these hydrodynamic modes,
out-of-equilibrium concentrations of ATP versus ADP
standard approaches consist in writing systematic expan-
and Pi . This parameter ∆µ is expressed as the differ-
sions in the different couplings that are allowed by the
ence in chemical potentials of ATP versus ADP plus Pi :
symmetry properties of the system. In the vicinity of a
∆µ = µATP −(µADP +µPi ). After identification of the dif-
critical point, which occurs generally when a continuous
ferent conjugated generalized fluxes and forces, that are
symmetry is spontaneously broken after a second-order
split into dissipative and reactive parts as a function of
phase transition has been traversed, the concept of renor-
their properties under time-reversal symmetry, the con-
malization group has given a theoretical framework to
stitutive equations that specify the dynamics are written
identify universality classes: starting from the full non-
in terms of a generalized Maxwell model, which describes
linear expansions of the underlying stochastic dynamics,
the viscoelastic dynamical properties of the gel. Under
only a few relevant parameters matter for the asymp-
its simplest form and for nonpolar viscoelastic gels, the
totic scaling laws that occur at the transition [274–276].
Maxwell model writes
Even though originally developed to study equilibrium
critical points, the renormalization-group concept has al-
D 0 1
lowed for the characterization of some out-of-equilibrium 1+τ σαβ = 2η vαβ − δαβ vγγ +η̄δαβ vγγ (11)
Dt d
universality classes (see e.g. [277–279] and the review
[280]). 0
in d dimensions. Here vαβ and σαβ are the symmetric
Away from such remarkable points however, any term parts respectively of the velocity-gradient tensor ∂α vβ
allowed by symmetry in a systematic expansion is a pri- and the viscous stress tensor, η and η̄ are respectively the
ori relevant. The standard approach for systems close to shear and bulk viscosities, and τ = E/η is the viscoelas-
thermodynamic equilibrium consists in writing general- tic relaxation time that is related to the Young elastic
23
modulus E and to the shear viscosity η. This relaxation mental literature. Finally, the description of spontaneous
time describes the crossover between an elastic behavior movements of thin layers of active gels has been applied
at short times that resembles that of a solid gel and a to the study of cell locomotion on a solid substrate that
viscous behavior at long times that resembles that of a occurs via the protrusion of the actin-filled lamellipodium
fluid[318]. Finally, D/Dt represents a convective corota- at the leading edge of the cell [258]. Reducing the lamel-
tional derivative that takes into account invariance with lipodium description to a two-dimensional gel protruding
respect to translations and rotations in the system. In the in one dimension, and with a spatially-dependent thick-
general framework of active polar gels close to thermo- ness, the steady-state thickness profile as well as the flow
dynamic equilibrium, generic linear couplings are added and force fields have been computed. One particularly
to this model following the general procedure described striking aspect of cell crawling that is described by this
above. Extensive presentations of the complete formal- formalism is the presence of a retrograde flow of the gel
ism can be found in refs. [255, 259], which also include as the cell is crawling. This aspect has been quantified in
discussions about its limitations and some of its possible earlier experiments performed on fish epidermal kerato-
extensions. In particular, in ref. [259], extensions that cytes [285]. It has been shown that while the cell is crawl-
aim to include the contributions of rotational viscoelas- ing, treadmilling of actin filaments happens faster than
ticity, of some nonlinear couplings and of passive as well global motion of the cell, such that the actin cortex is
as active sources of noise are briefly discussed. The main moving rearward with respect to the substrate, in a direc-
developed extension so far concerns the generalizations tion opposite to the movement of the cell [94, 286, 287].
of this formalism to multi-component active gels that are Similar questions have been addressed using different the-
now being developed [260, 283]. These allow in partic- oretical frameworks in [288–290].
ular to take into account the possible permeation of the
cytosol through the cytoskeletal gel, which affects force
balance in the system, and which might be of importance D. Comparisons of the different approaches to
for cell motility. describing active polymer solutions
Despite its recent development, this generic theory of
active polar gels has been applied to the description of With these different ways of approaching the descrip-
some systems that are of particular relevance for cell tion of the dynamics of the cell cytoskeleton as a whole,
motility or experimental situations observed in vitro. Its a natural question is to ask to what extent these dif-
first application was the study of topological defects in ferent approaches are similar and different, and which
the polarity field of the gel that lead to the formation aspects of the cytoskeleton or cell behavior can be or
of patterns such as asters, vortices and spirals [254]. As not described by each of the theories. For answer-
a function of two dimensionless parameters representing ing these questions, connections between the different
the relative strength of the coupling to the chemical po- approaches have been made, first between mesoscopic
tential ∆µ and to the bend and splay moduli of the po- and hydrodynamic descriptions [261, 291]. In [261], a
lar gel, a phase diagram was derived where vortices and generalization of the mesoscopic model introduced in
asters give rise to rotating spirals via dynamic instabili- [237, 238] is developed to obtain a set of continuum equa-
ties. These relate to the spatial patterns that have been tions in unconfined geometries. A phase-diagram is de-
observed in vitro [232, 233], as well as to the creation rived that results from the stability analysis of the ho-
of spontaneous motion, of most relevance for cell motil- mogeneous state of actively cross-linked polymers, tak-
ity. In a different geometry, namely a cylinder of finite ing into account excluded-volume interactions and es-
diameter and length, the formalism has been applied to timates of entanglement in two and three dimensions.
establish a phase diagram of ring formation that contains It is found that an instability occurs as the bundling
phases of one or multiple rings, and which can be quies- rate between filaments of the same orientation is in-
cent or oscillating [256]. This is relevant for understand- creased, which at low filament density happens first via a
ing the formation and localization of cortical rings that density-fluctuation instability, and at high filament den-
form prior to cytokinesis and for which double-ring for- sity via an orientational-fluctuation instability. In the
mation has been observed with certain plant cells [284]. presence of a finite sorting rate between filaments of dif-
To understand the generation of active flows that might ferent orientations, propagating modes appear that re-
be of relevance for cell crawling, a generic phase diagram flect oscillatory behavior. In [291], the continuum theory
has been derived for a two-dimensional active polar film is related to nonlocal descriptions of filament-motor sys-
that is compressible [257]. Compressibility here might tems, since filaments can transmit stresses over finite dis-
refer to different thicknesses in a three-dimensional in- tances. The effective parameters of the continuum theory
compressible gel that is described in two dimensions after are recovered from the previously-published mesoscopic
integration of the density fields over its thickness. Within description [237], even though with missing coefficients
this framework, density fluctuations couple generically to that are thought to correspond to microsocpic multi-
polarity splay, and different topological phases of the gel- particle interactions, not described in [237]. Effects of
polarity organization are found that could correspond to polymerization-depolymarization dynamics via effective
some of the previously-observed patterns in the experi- source and sink terms in the local filament densities are
24
also discussed (see also [260, 283]) - like it is the case in VIII. EXTENSIONS AND FUTURE
the effective macroscopic theories - as well as the role of DIRECTIONS
polarity. In particular, it is found that nonpolar arrange-
ments of filaments do not exhibit oscillatory instabili- Cell motility is a complex and integrated process that
ties and propagating modes, which might be of relevance relies on self-organization of the cytoskeleton, carefully
for muscle sarcomeric structures. As seen previously, in and precisely orchestrated by the cell with the help of
these systems, spontaneous oscillations that have been numerous different types of molecular players. If one in-
observed correspond more to oscillatory instabilities of cludes the subcellular movements that are responsible for
rigidly-coupled collective motors than to solitary-wave intracellular traffic and material exchange between the
solutions, as they are found in systems of active polar inner parts and external parts of the cell, cell-motility
filaments. mechanisms are found to ground the activity of all life
forms on earth. When looked under the microscope,
motility mechanisms and structural changes of the di-
verse cell types appear so vast and various that a compre-
hensive understanding of their underlying mechanisms
Microscopic theories present the advantage of being seems to be an overwhelming challenge. However, as we
able in principle to give rise to a full description of have seen from the literature covered in the present arti-
a given system with arbitrary precision and specificity, cle, our understanding of cell motility has tremendously
and to take into account the nonlinear effects that are progressed over the past two decades. On the one hand,
of direct relevance for the system’s behavior. However, complexity has even further emerged, since the biochemi-
they rely on the microscopic knowledge that one has on cal characterization of the molecular players involved has
the system under consideration, and are therefore lim- revealed that at least hundreds of different protein types
ited by the available information on the different agents. participate in the structural and dynamical organization
In addition, they end up with effective descriptions that of the cell cytoskeleton. On the other hand, despite the
are model-dependent, in that the different parameters of existence of such very complex regulation processes that
the so-obtained theory, which describe its physical be- rely on the integrated interplay of the whole set of dif-
havior, depend on the interactions that are taken into ferent molecular players, the characterization of the cell
account at the microscopic level. Also, an important cytoskeleton has revealed that its main structures and
aspect of active cytoskeleton dynamics that is usually functions are due to just a few types of key proteins,
not described in such microscopic approaches is the very namely three types of biopolymers and three superfami-
important phenomenon of treadmilling that relies on lies of molecular motors. Even more striking is the evo-
polymerization-depolymerization dynamics of cytoskele- lutionary conservation of the main molecular players in-
tal polymers, and which we have seen to be of crucial im- volved in building the cytoskeleton dynamical filaments,
portance for some mechanisms of cellular motility such as both within the eukaryotic domain of life on the direct se-
Listeria propulsion or nematode-sperm-cell locomotion quence point of view, and even across the three domains
(see Section V). However, despite the absence of these of life when structural and functional properties are con-
effects, which are taken into account effectively in macro- sidered. These striking observations indicate that the dif-
scopic hydrodynamic descriptions, such microscopic ap- ferent underlying mechanisms of cell motility all rely on
proaches allow for the derivation of the forces exchanged generic principles that can be understood on a biophys-
between the motors and the filaments from microscopic ical point of view. In addition, further help from micro-
knowledge, while they appear as effective parameters of manipulation and fluorescence-microscopy techniques, as
unknown explicit origin in effective macroscopic descrip- well as the development of simplified systems based on
tions. Thereby, questions can be addressed that con- gene-expression control and bio-mimetic artificial sys-
cern the role played by the specific physical properties tems, has enabled the experimental biophysical investi-
of motor-filament interactions at the microscopic level gation of the different specific aspects of the processes at
in controlling the system behavior on large scales. In- play.
deed, the richness of the observed self-organized struc- The theoretical analyses reviewed in this article have
tures raises the question of how much is generic, and shown that central concepts that underly the cytoskele-
how much is specific in cytoskeleton behavior. For ex- ton dynamics are self-organization and dynamic instabil-
ample, experiments have shown that very different self- ities, here grounded on out-of-equilibrium nonlinear dy-
organizing structures occur with processive as opposed namics’, thermodynamics’ and statistical physics’ prin-
to non-processive motor proteins: at high motor concen- ciples. Such concepts are at the basis of all the the-
trations, microtubule-kinesin mixtures self-organize in a oretical approaches that have been developed to un-
variety of spatial patterns [232, 233], as homogeneous derstand the mechanisms of diverse phenomena such
states are more robust with acto-myosin systems [139], as polymerization-depolymerization force and movement
an effect that can be thought of as the influence of mo- generation, molecular motors’ individual behaviors and
tor processivity on the dynamical large-scale parameters collective phenomena, as well as the generic behaviors
[261]. of active-polymer solutions which lead to a description
25
of the cytoskeleton dynamics as a whole. On all of cytoskeleton-based pattern formations (see e.g. [293]),
these topics, microscopic as well coarse-grained effective and could play a crucial role in driving other cytoskele-
macroscopic approaches have been developed. As al- tal self-organization phenomena, especially close to dy-
ready discussed, they both have their advantages, powers namical instabilities, where the effect of noise is high-
and limitations, and represent important complementary est. Finally, having at hand the underlying biochemical
steps in the ultimate goal of an integrated description of and biophysical mechanisms of cell forces and motility, a
the universal principles that underly cell motility. great challenge is to understand self-organization at yet
As we have seen in this article, our understanding of larger scales, namely in animal tissues, where collections
cell motility and cell cytoskeleton dynamics has grandly of cells present integrated coherent behaviors that drive
benefitted from the interplay between experiments and diverse key processes such as morphogenesis, wound heal-
modeling, each for its own reasons guiding the other in ing, immune response, tumor development and metas-
its directions of investigation. To further understand the tases formations. There, the same scheme involving “mi-
integrated processes at play in cell motility, such fruit- croscopic” as well as effective “macroscopic” approaches
ful interactions will certainly be further required and can certainly play an equally major role, “microscopic”
developed. On the theoretical point of view, bridges approaches then potentially integrating the whole knowl-
between understanding simplified systems or some par- edge acquired at the level of a single cell, and partially
ticular aspects of cell motility and the phenomenon of reviewed in this article.
cell motility as a whole at the global cellular level, have
already started being investigated, but further develop-
ments of these two different ways of approaching the cy-
toskeleton dynamics as well as understanding the links Acknowledgments
that ultimately relate them are required. Another im-
portant aspect whose understanding represents a chal- To write this article, I grandly benefited from Karsten
lenge is the potentially crucial role of noise that has Kruse’s habilitation thesis, which constituted a very good
been so far most of the time absent from the macro- starting point as an extensive review of the existing
scopic effective theoretical approaches. Indeed, noise biophysical literature on the cytoskeleton. I acknowl-
in nonlinear dynamical systems is known to potentially edge Cécile Sykes and Jean-François Joanny for discus-
have important constructive effects, whose main repre- sions, careful reading of the manuscript and constructive
sentatives are stochastic resonance, coherence resonance criticisms and suggestions. I also acknowledge Andrew
and noise-induced transitions, as well as the extensive Callan-Jones for pointing to me important references.
gallery of different spatially-extended phenomena such
as array-enhanced stochastic and coherence resonance,
or noise-enhanced synchronization of nonlinear oscilla-
tors (see e.g. [292]). Such phenomena have already been IX. BIBLIOGRAPHY
recognized to play an important role in some biological
[286] C. H. Lin, E. M. Espreafico, M. S. Mooseker, and - to drive many chemical reactions in the cell.
P. Forscher, Neuron 16, 769 (1996). [304] Animated movies of this process can be seen at
[287] F. Coussen, D. Choquet, M. P. Sheetz, and H. P. Erick- http://www.uni-leipzig.de/ pwm/kas/actin/actin.html
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[289] B. Rubinstein, K. Jacobson, and A. Mogilner, Multi- [305] Illustrations of these structures can be found at
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[290] M. M. Kozlov and A. Mogilner, Biophys. J. 93, 3811 [306] Similarly to ATP, GTP is a stored source of energy for
(2007). the cell that is consumed via a hydrolysis reaction, here
[291] K. Kruse, A. Zumdieck, and F. Jülicher, Europhys. Lett. GTP
GDP + Pi .
64, 716 (2003). [307] Animated movies of myosin skeletal
[292] A. Pikovsky, M. Rosenblum, and J. Kurths, fibers’ detailed motion can be seen at
Synchronization-A Unified Approach to Nonlinear http://www.scripps.edu/cb/milligan/research/movies/myosin.m
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128102 (2003). [309] Animated movie of kinesin’s de-
[294] J. Lee, A. Ishihara, and K. Jacobson, Symp. Soc. Exp. tailed motion can be seen at
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[296] See, for example, http://www.cytoskeletons.com/database.php. found at http://www.proweb.org.
[297] Note that some zoologists also use the term “pseudopo- [311] In addition to Arp2 and Arp3, which are members of the
dia” or “pseudopods” rather generally to refer to a va- Actin related proteins (Arp) family in that they have
riety of cell-surface protrusions. These include the dif- sequences and structures that are similar to actin, the
ferent types of protrusions described here as playing a Arp2/3 complex contains five other smaller proteins.
role in amoeboid motility, but also the long extended [312] Up-to-date informations can be found at
processes that some cell types use only as feeding appa- http://www.bms.ed.ac.uk/research/others/smaciver/Cyto-
ratus, like axopodia. Topics/actinpage.htm.
[298] A short video of a locomoting Amoeba pro- [313] See the movies associated with ref [82], as well as the
teus can be seen on the following website: one of a neutrophil cell that chases a bacterium at
http://www.bms.ed.ac.uk/research/others/smaciver/A.prot.Loc.mov.http://www.biochemweb.org/fenteany/research/cell migration/
[299] Fibroblasts are the cells that synthesize and maintain [314] For an animated illustration, see
the extracellular matrix in most animal connective tis- http://www.jhu.edu/cmml/movies/anim/eBRatchet2.swf.
sues. They provide a structural framework (stroma) for [315] For an introduction to the elasticity of continuous me-
many tissues, and play a crucial role in wound healing. dia, see, e.g., [295].
Keratocytes are epithelial cells that have been charac- [316] An illustration of a paramecium can be seen in Fig. 1,
terized in the epidermis of fish and frogs, and that have center.
been named so because of their abundant keratin fila- [317] The next momentum qαβ = huα uβ − d−1 p2 δαβ i, where
ments. They are specialized in wound healing, and are d is the dimension of space, is a symmetric traceless
one of the most spectacular example of fast and persis- tensor of order two that corresponds to nematic order.
tent locomotion in cells, with velocities up to 30 µm/min [318] Note that only one relaxation time is assumed to char-
[1, 294]. acterize the system, as some experiments suggest that
[300] Growth cones are structures that are found at the tip a power-law distribution of relaxation times is better
of axons and dendrites, by means of which neuron cells suited to describe cytoskeleton dynamics, potentially
extend. because of some scale-invariant dynamical properties in
[301] Cell-motility videos can be seen at the system [146, 147].
http://cellix.imba.oeaw.ac.at.
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31