CYTOSKELETON AND

CELL MOTILITY
Stephen William Hawking CH
CBE FRS FRSA
■ English theoretical
physicist, cosmologist, and
author who was director of
research at the Centre for
Theoretical Cosmology at
the University of
Cambridge at the time of
his death
Genetic diseases due to defect on
cytoskeleton

■ Abnormalities of neurofilaments
underlie the loss of motor
control in Lou Gehrig’s disease
(ALS) and the motor neuron
disease that afflicts the
physicist Stephen Hawking.
Cytoskeleton

■ Structure
– network of fibers extending throughout
cytoplasm
– 3 main protein fibers
■ microfilaments
■ microtubules
■ intermediate filaments
Cytoskeleton

■ Function
– structural support
■ maintains shape of cell
■ provides anchorage for organelles
– motility
■ cell locomotion
■ cilia, flagella, etc.
– regulation
■ organizes structures &
activities of cell
Microfilament (Actin
Filament)
■ Structure
– thinnest class of fibers
– solid rods of protein, actin
– twisted double chain of actin
subunits
– about 7nm in diameter
■ Function
– 3-D network inside cell
membrane
– in muscle cells, actin
filaments interact with myosin
filaments to create muscle
contraction
Actin filament

■ Function : in cell division and cell motility

■ Dynamic process
– actin filaments constantly form & dissolve
making the cytoplasm liquid or stiff during
movement
■ movement of Amoeba
■ cytoplasmic streaming in animal cells
– speeds distribution of materials
■ The Actin cytoskeleton plays a
major role in cell motility.
– involves both changes in
cell location and limited
movements of parts of the
cell.
■ cytoskeleton moves as cell
mobile
The function of actin filament are
inhibited by both polymer stabilizing
dan –destabilizing chemicals
Actin and Myosin

■ First motor protein to be

identified –skeletal muscle
myosin generate force for
contraction
■ each myosin head bind
and hydrolyze ATP, using
energy of ATP hydrolysis
to walk toward the + end of
actine filament.
Sliding of Myosin II along AF causes
muscle to contract

■ In vertebrate : running, walking, flying depens on rapid

contraction of skeletal muscle.
■ However involuntary movement heart pumping dan
gut peristaltic depend on contraction of cardiac muscle
and smooth muscle. All of this muscle contraction
depend on ATP-sliding of actin against array of myosin
II filament.
■ Motor molecules also carry vesicles or organelles
(mitochondria, golgi stack, secretory vesicles) to various
destinations along “monorails’ provided by the
cytoskeleton.
■ Interactions of motor proteins and the cytoskeleton
circulates materials within a cell via streaming.
■ In muscle cells, thousands of actin filaments are
arranged parallel to one another.
■ Thicker filaments, composed of a motor protein,
myosin, interdigitate with the thinner actin fibers.
– Myosin molecules walk along the actin filament, pulling stacks of
actin fibers together and shortening
the cell.

Fig. 7.21a
■ In other cells, these actin-myosin aggregates are less
organized but still cause localized contraction.
– A contracting belt of microfilaments divides the
cytoplasm of animals cells during cell division.
– Localized contraction also drives amoeboid movement.
■ Pseudopodia, cellular extensions, extend and contract through the
reversible assembly and contraction of actin subunits into microfilaments.

Fig. 7.21b
Cytoskeleton related
diseases
■ Mutations in MT or AF-associated motor proteins
have been linked to neuron degenerative
disorders and other human diseases.
■ Motor proteins drive cellular transport in
functioning of neurons where the cell body is
distant from the synapse, and molecules must
travel incredible distances for proper function.
Dysfunctional axonal transport has been linked to
human diseases such as Parkinson’s and Alzheimer’s
disease.
Microtubule

■ Structure
– thickest fibers
– hollow rods about 25nm in diameter
– constructed of protein, tubulin
– grow or shrink as more tubulin molecules are
added or removed
microtubule

■ Influence by binding
and hydrolysis of GTP.
GTP hydrolysis occur
within beta tubulin
■ Free PO4 group are
released
Function

■ Move chromosomes during cell division

– centrioles
■ Fast axonal transport, rapid movement of
mitochondria, secretory vesicle precursor and various
synapse component
■ tracks that guide motor proteins carrying organelles
to their destination
– motor proteins: kinesin & dynein
■ motility
– cilia
– flagella
Microtubulus and motor
move organelles and vesicle

■ Major function of
cytoskeletal motor in
interphase is transport
and positioning
membrane enclosed
organela
Centrioles

■ Cell division
– in animal cells, pair of centrioles
organize microtubules guiding
chromosomes in cell division
■ During animal cell division, the centrioles
replicate and the CT divides → two CT, each
with its own pair of centrioles. The two CT
move to opposite ends of the nucleus, and
from each CT, MT grow into a "spindle"
which is responsible for separating
replicated chromosomes into the two
daughter cells.
◼ 3. Important component of cell division
Transport material of axons via
microtubule

❖ A Neuron must be
supplied with new
materials- to an axon
terminal to replenish those
lost in exocytosis of
neurotransmitters at
(synapse).
❖ protein and membrane
must be transported
through axon to synaptic
region. accomplished on
microtubule
Microtubule and Intracellular
transport

■ 2 familes of motor protein-

kinesins and dyneins
mediate transport along
microtubules.

■ Motor protein cause

cytoskeletal filament to
exert tension or to slide
against each other
CILIA AND FLAGELLA

■ Extensions of eukaryotic cytoskeleton

■ Cilia = numerous & short (hair-like)
■ Flagella = 1-2/cell & longer (whip-like)
– move unicellular & small multicellular organisms by
propelling water past them
– cilia sweep mucus & debris from lungs
– flagellum of sperm cells
Cilia

■ Oar-like movement
– alternating power & recovery strokes
– generate force perpendicular to cilia’s axis
Flagella

■ undulatory movement
– force generated parallel to flagellum’s axis
 Cilia and Flagella

■ Structure
– formula 9+2!
– 9 pairs of microtubules
around 2 single
microtubules in center
– bending of cilia & flagella
is driven by motor
protein (dynein_
Intermediate filament
■ Structure
– specialized for bearing tension
– built from keratin proteins
■ same protein as hair
– intermediate in size 8-12nm

■ Function
– hold “things” in place inside cell
– more permanent fixtures of cytoskeleton
– reinforce cell shape & fix organelle
location
■ nucleus is held in place by a network of
intermediate filaments
Intermediate Filament

■ Function: Support the nuclear membrane and help

connect cells into tissues.
■ IF typically crisscross the cytosol, forming an internal
framework that stretches from the nuclear envelope to
the plasma membrane. IF is located adjacent to
cellular membranes-> nuclear lamina, is anchored to
the inner nuclear membrane by prenyl anchors on
lamin B.
■ AF fills the cytosol and anchores the cell to the
substratum. ex. in platelets, epithelial cells and muscle
Placement organella in the cell
 Structure of an intermediate filaments
Monomer

Parallel dimer

Antiparallel
tetramer

Protofilaments

Intermedaite
filaments

Molecular Biology of the Cell (© Garland Science 2008)

Role of intermedier filaments

Buffer against external mechanical stress

Tissue specificity !!!

Epithel – keratin
Vimentin
Connective tissue
Muscles
Neuroglia
} vimentin-like
Desmin
Glial protein

Neurones(axon) - neurofilaments

Exception:
Nucleus – lamines (A,B,C) →(lamina fibrosa)
 Axon of a neuron Glial cell Axon cross-section
Neurofilament (NF-H) Glial filaments

Cross bridges are few cross bridges

formed by non-helical C
terminus

Molecular Biology of the Cell (© Garland Science 2008)

◼ Function: Support the nuclear membrane and
help connect cells into tissues.
◼ IF typically crisscross the cytosol, forming an
internal framework that stretches from the
nuclear envelope to the plasma membrane.
◼ IF is located inside nucleus is called nuclear
lamina. Providing mechanical support, regulates
important cellular events such as DNA
replication and cell division. is anchored to the
inner nuclear membrane by prenyl anchors on
lamin B.
■ Formed by a large, heterogeneous group of
proteins
At least 4 major filament types
– Keratin - epithelial cells
– Neurofilaments – neurons
– Vimentin-containing filaments – fibroblasts,
glial cells, muscle cells
– Nuclear lamina – all nucleated cells
Intermediate filaments in kidney cell (left, green) and
cultured epithelial cell (right, orange; desmosomes are
green)
Keratin

■ Keratins are the main intermediate filament

proteins of epithelial cells. In keratinocytes of
the mammalian epidermis they form
a cytoskeleton that resists mechanical stress.
■ Keratin filament impart mechanical strength to
epithelial tissue in part by anchoring the IF at
sites of cel-cell contact (desmosomes), or cell-
matrix contact (hemidesmosome).
■ Mutation of keratin gene causes
peel skin (epidermolysis
bullossa simplex). Defective
keratine are epressed in the
basal cell layer of epidermis.
neurofilament

■ Member of IF – neurofilament are

found in high conc along axon..
■ Neurodegenerative disease ALS is
associated ith an accumulation of
and abnormal assembly of
neurofilament in motor neuron cell
bodies and in axon.
Cell migration

example
■ Macrophage and neutrophil into site of infection
■ Osteoclast tunnel into bone
■ Fibroblast migrate ito conecctive tissue,
remodelling of damage structures at site of injury
■ The Actin cytoskeleton plays a
major role in cell motility.
– involves both changes in
cell location and limited
movements of parts of the
cell.
■ cytoskeleton form
polymerization as cell migrate
■ And disassembly at new site.
■ Cell migration is a complex process that
depends on the actin rich cortex beneath the
palsma membrane.
Including:
■ Protrution (plasma embrane is pushed out in the
front of membrane)
■ Attachment (actin connect across the PM to
substratum)
■ Traction (the bulk of trailing cytoplasm is drawn
forward)
• Microfilament and membrane binding protein
form a skeleton underlying the plasma
membrane.
END
Thank you