Module 10: Membrane Biophysics

1. What are the different physical concepts the govern cellular membrane activities? (cite the
concepts and explain its application to cellular activities)
Plasma Membrane and Its Function
Plasma membranes are continuous, unbroken sheets and, as such,
inevitably enclose compartments. The plasma membrane encloses the
contents of the entire cell, whereas the nuclear and cytoplasmic
membranes enclose diverse intracellular spaces. The various
membrane-bounded compartments of a cell possess markedly
different contents. Membrane compartmentalization allows
specialized activities to proceed without external interference and
enables cellular activities to be regulated independently of one
another. Also, plasma membranes not only enclose compartments but
are also a distinct compartment themselves. As long as reactants are
present in solution, their relative positions cannot be stabilized and
their interactions are dependent on random collisions. Because of
their construction, membranes provide the cell with an extensive framework or scaffolding within
which components can be ordered for effective interaction. They prevent the unrestricted exchange of
molecules from one side to the other. At the same time, membranes provide the means of
communication between the compartments they separate. The plasma membrane, which encircles a
cell, can be compared to a moat around a castle: both serve as a general barrier, yet both have gated
“bridges” that promote the movement of select elements into and out of the enclosed living space.
Significantly, the plasma membrane contains the machinery for physically transporting
substances from one side of the membrane to another, often from a region where the solute is present
at low concentration into a region where that solute is present at much higher concentration. The
membrane’s transport machinery allows a cell to accumulate substances, such as sugars and amino
acids, that are necessary to fuel its metabolism and build its macromolecules. The plasma membrane
is also able to transport specific ions, thereby establishing ionic gradients across itself. This capability
is especially critical for nerve and muscle cells. Likewise, they play a critical role in the response of a
cell to external stimuli, a process known as signal transduction. Membranes possess receptors that
combine with specific molecules (ligands) or respond to other types of stimuli such as light or
mechanical tension. Different types of cells have membranes with different receptors and are,
therefore, capable of recognizing and responding to different environmental stimuli. The interaction
of a plasma membrane receptor with an external stimulus may cause the membrane to generate a
signal that stimulates or inhibits internal activities. For example, signals generated at the plasma
membrane may tell a cell to manufacture more glycogen, to prepare for cell division, to move toward
a higher concentration of a particular compound, to release calcium from internal stores, or possibly
to commit suicide.
Phospholipids: The Main Lipid Constituents of Most Bio membranes and their Assemble
The fundamental building blocks of all cell
membranes are phospholipids, which are amphipathic
molecules, consisting of two hydrophobic fatty acid chains
linked to a phosphate-containing hydrophilic head group.
Because their fatty acid tails are poorly soluble in water,
phospholipids spontaneously form bilayers in aqueous
solutions, with the hydrophobic tails buried in the interior
of the membrane and the polar head groups exposed on
both sides, in contact with water. Such phospholipid
bilayers form a stable barrier between two aqueous
compartments and represent the basic structure of all biological membranes. An important property of
lipid bilayers is that they behave as two-dimensional fluids in which individual molecules (both lipids
and proteins) are free to rotate and move in lateral directions. Such fluidity is a critical property of
membranes and is determined by both temperature and lipid composition. For example, the
interactions between shorter fatty acid chains are weaker than those between longer chains, so
membranes containing shorter fatty acid chains are less rigid and remain fluid at lower temperatures.
Lipids containing unsaturated fatty acids similarly increase membrane fluidity because the presence
of double bonds introduces kinks in the fatty acid chains, making them more difficult to pack
together. Because of its hydrocarbon ring structure, cholesterol plays a distinct role in determining
membrane fluidity. Cholesterol molecules insert into the bilayer with their polar hydroxyl groups
close to the hydrophilic head groups of the phospholipids. The rigid hydrocarbon rings of cholesterol
therefore interact with the regions of the fatty acid chains that are adjacent to the phospholipid head
groups. This interaction decreases the mobility of the outer portions of the fatty acid chains, making
this part of the membrane more rigid. On the other hand, insertion of cholesterol interferes with
interactions between fatty acid chains, thereby maintaining membrane fluidity at lower temperatures.

Membrane Permeability and Its Energetics; Growth of Biomembrane

All cells are contained by a cell membrane (biomembrane) selectively open to some chemicals
and ions but acts as a barrier to undesired components. To put it another way, biomembranes are
enclosing membranes which function as selectively permeable barriers to chemicals and ions. It
should be noted though that the title biomembrane may denote a wide range of definitions; especially,
cellular membranes should not be confused with isolating tissues formed by layers of cells (e.g.,
mucous membranes). Small polar molecules can sometimes pass easily (e.g. ethanol), but more often
pass at low rates if at all (e.g. water). However, small nonpolar molecules are able to pass through the
membrane with relative ease. The reasons should be self-evident: larger molecules simply cannot fit
between the lipid molecules to make their way through. Small molecules that can fit must be
hydrophobic, otherwise the fatty acyl core of the membrane will repel them and block them from
proceeding. Higher concentrations of cholesterol, by filling in gaps between phospholipid tails,
decreases permeability even for small molecules that can normally pass through the membrane easily.
Cells need far more than small nonpolar molecules for their material and energy requirements.
Fortunately for life on Earth, the membranes of living cells are not purely phospholipids, and as we
will see, proteins embedded in the phospholipid bilayer can form conveyances for the transport of
many different molecules in and out of the membrane.
There are two major ways that molecules can be moved across a membrane, and the distinction
has to do with whether or not cell energy is used. Passive mechanisms like diffusion use no energy,
while active transport requires energy to get done.
Active Transport is the biological process in which molecules move against the concentration
gradient and require chemical energy to move biochemical compounds from a lower region to the
high region. Therefore, this process uses ATP – Adenosine triphosphate to pump molecules through a
concentration gradient. Complex sugar, ions, large cells, proteins, and other particles are transported
in this process. Meanwhile, Passive Transport, energy is not required for transporting the molecules,
as the biochemical move from a region of higher concentration to a region of lower concentration. All
particles which are easily soluble are transported through passive transport. This process is carried out
to maintain the balance and the equilibrium level in a cell. All the wastes molecules including, water
and carbon dioxide is separated and moved out of the cell using passive transport. Meanwhile,
nutrients like oxygen that are functional for the cell are diffused in this process. Osmosis, diffusion
and facilitated diffusion are some of the examples of passive transport.
Growth of the plasma membrane is as fundamental to cell reproduction as DNA replication,
chromosome segregation and ribosome biogenesis, yet little is known about the underlying
mechanisms. Membrane growth during the cell cycle requires mechanisms that control the initiation,
location, and extent of membrane growth, as well as mechanisms that coordinate membrane growth
with cell cycle progression. Exocytosis is a general term used to denote vesicle fusion at the plasma
membrane, and it is the final step in the secretory pathway that typically begins in the endoplasmic
reticulum (ER), passes through the Golgi apparatus, and ends at the outside of the cell. Endocytosis
refers to the recovery of vesicles from the plasma membrane. Exocytotic vesicle fusion involves the
coalescence of vesicle and plasma membranes and allows the so-called fusion pore to form. The
fusion pore is a channel that passes through the vesicle and plasma membranes and allows delivery of
the vesicle contents to the extracellular compartment. Docking is the process by which the exocytotic
vesicle is fixed beneath the plasma membrane before fusion. It is generally believed to involve
molecular recognition between vesicle and plasma membrane and is therefore one aspect of vesicle
targeting. Another kind of targeting can be provided by the cytoskeletal proteins that move vesicles
around the cell. Sorting is a term that can be applied to vesicles, in which case it simply describes the
consequences of targeting. Sorting has a more useful and distinct meaning when applied to vesicle
contents: these contents vary according to the destination of the vesicle and the state of differentiation
of the cell. Sorting of contents can occur in the ER or Golgi or post-Golgi compartments, as can
processing, in which polysaccharides or proteins are modified enzymatically into their mature form,
ready for delivery.

http://dosequis.colorado.edu/Courses/MCDB3145/Docs/Karp-120-171.pdf
https://www.khanacademy.org/test-prep/mcat/cells/transport-across-a-cell-membrane/a/passive-
transport-and-active-transport-across-a-cell-membrane-article
http://www.plantcell.org/content/11/4/643
https://phys.libretexts.org/Courses/University_of_California_Davis/UCD%3A_Biophysics_241_-
_Membrane_Biology/04%3A_Membrane-
Protein_Interactions/4.01%3A_Membrane_Permeability#:~:text=The%20permeability%20of%20a
%20membrane,permeated%20molecules%20across%20the%20biomembrane.

Physics of Cell Wall and Osmotic Pressure

It is generally accepted that the fundamental behavior underlying all rapid plant growth is an
irreversible stretching of primary cell walls due to mechanical loads generated by cell turgor pressure.
Turgor pressure, the osmotically maintained hydrostatic pressure in living plant cells, and the
mechanics of the cell wall itself, are undoubtedly among the most fundamental physical factors that
dictate both cell growth and cell morphologies in plants (Zonia and Munnik, 2007). During plant cell
growth, the cell wall system performs seemingly contradictory roles. On the one hand, it must be
rigid enough to allow turgor pressure to build up, while on the other, it must be loosened in some way
to permit cell enlargement during growth.
The physics underlying wall extension growth appears to be distinct from the biochemical events
that constitute the broader background for all cell growth. While the study of biochemical precursors
and cross-linkages emphasizes the importance of enzymatic activities such as the synthesis of wall
components and the cleavage of hemicellulose tethers, etc., the biophysical approach focuses on the
purely physical aspects of extension growth (e.g. wall stresses and strains, mechanical properties of
the walls, and cell geometry). Obviously, an understanding of the physical principles underlying wall
stress relaxation is essential to understanding the full spectrum of wall behaviors during growth. The
biochemical approach to cell wall loosening has made notable advances in recent years (Cosgrove,
2006). However, our appreciation of the physical aspects of the process remains basically unchanged
since the 1960s (Probine and Preston, 1962; Lockhart, 1965a, 1965b; Cleland, 1967; Ray et al.,
1972).
In actively growing cells, because the walls are thin compared to the size of the cell, tensile
stresses in the walls can be very high. Typical plant cell turgor pressures in the range of 0.3 to 1.0
MPa translate into between 10 and 100 MPa of tensile stress in the walls. In this regard, early students
of the problem including Probine and Preston (1962), Lockhart (1965a), Cleland (1967), and also Ray
et al. (1972) all recognized that cell enlargement begins with stress relaxation in the walls. They
interpreted stress relaxation as a viscoelastic/creep-based process. Accordingly, most of the relevant
experimental work on plant materials has been carried out under this viscoelastic/creep paradigm.
(Published November 2007. DOI: https://doi.org/10.1104/pp.107.101964)
(http://www.plantphysiol.org/content/145/3/763)

Intracellular Motion

Cell movement is a complex and dynamic process that causes changes in cell morphology by
reorganizing the actin cytoskeleton and modulating cell adhesions. For directional cell migration,
cells must continuously receive the polarized environmental signals and transmit the polarized
intracellular signals from a fixed direction, which orient protrusion of the leading edge. The dynamic
regulation of cyclical activation and inactivation of the Rho family small G proteins as a result of the
crosstalk between small G protein signaling pathways is particularly important for the formation and
disassembly of leading edge structures. However, the regulatory mechanisms of directionality and
small G protein dynamics have not been fully understood. Recently, it has been found that  nectin, an
immunoglobulin-like cell adhesion molecule, implicated in a wide variety of fundamental cellular
events including cell adhesion, proliferation, movement, and polarity, and its related proteins such as
nectin-like molecule-5 and afadin regulate directionality and small G protein dynamics during
directional cell movement.

Thermodynamics inside the Cell

Over the past century relatively little attention has been paid to the physical basis of embryology.
With the discovery through the space program that the very important cytoskeletal proteins, such as
microtubules, are differentially sensitive to gravity (Portet et al., 2003), it is clear that the
fundamental conceptual basis of embryology cannot be developed merely by employing a classical
molecular genetic framework. In addition to gravity, other physical forces such as surface tension due
to intercellular adhesion (Goel et al., 1970, 1975; Gordon et al., 1972, 1975; Steinberg, 1996;
Trinkaus, 1984a), the mechanical forces exerted during cell division (Rappaport, 1996), and physical
waves of cytoskeletal expansion and contraction that traverse embryos (Gordon, 1999) all provide
important non-chemical contributions to morphogenesis of embryos. Moreover, cell differentiation
leading to morphological differences between cells in various tissues and organs are extreme
examples of what appears to be an entropy reduction process, i.e. self-organization. This apparent
contradiction of the second law of thermodynamics drew attention of many physicists beginning with
Schrödinger (1967). At the macroscopic level, living systems are thermodynamically open and far-
from-equilibrium systems, hence the balance of entropy at this level must necessarily involve
metabolic energy production as well as heat and waste product dissipation into the external
environment.