Cell membrane permeability and functions

SH/LECTURE NOTES CELL BIOLOGY
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CELL MEMBRANE STRUCTURE
& FUNCTION

SH/LECTURE NOTES CELL BIOLOGY 1
The Cell Membrane
A cell’s plasma membrane defines the boundary of the cell and determines the nature of
its contact with the environment. Cells exclude some substances, take in others, and
excrete still others, all in controlled quantities. Plasma membranes enclose the borders
of cells, but rather than being a static bag, they are dynamic and constantly in flux. The
plasma membrane must be sufficiently flexible to allow certain cells, such as red blood
cells and white blood cells, to change shape as they pass through narrow capillaries.
These are the more obvious functions of a plasma membrane. In addition, the surface of
the plasma membrane carries markers that allow cells to recognize one another, which
is vital as tissues and organs form during early development, and which later plays a role
in the “self” versus “non-self” distinction of the immune response.
The plasma membrane also carries receptors, which are attachment sites for specific
substances that interact with the cell. Each receptor is structured to bind with a specific
substance. For example, surface receptors of the membrane create changes in the
interior, such as changes in enzymes of metabolic pathways. These metabolic pathways
might be vital for providing the cell with energy, making specific substances for the cell,
or breaking down cellular waste or toxins for disposal. Receptors on the plasma
membrane’s exterior surface interact with hormones or neurotransmitters, and allow
their messages to be transmitted into the cell. Some recognition sites are used by
viruses as attachment points. Although they are highly specific, pathogens like viruses
may evolve to exploit receptors to gain entry to a cell by mimicking the specific
substance that the receptor is meant to bind. This specificity helps to explain why human
immunodeficiency virus (HIV) or any of the five types of hepatitis viruses invade only
specific cells.
Fluid Mosaic Model
In 1972, S. J. Singer and Garth L. Nicolson proposed a new model of the plasma
membrane that, compared to earlier understanding, better explained both microscopic
observations and the function of the plasma membrane. This was called the fluid mosaic
model. The model has evolved somewhat over time, but still best accounts for the
structure and functions of the plasma membrane as we now understand them. The fluid
mosaic model describes the structure of the plasma membrane as a mosaic of
components—including phospholipids, cholesterol, proteins, and carbohydrates—in
which the components are able to flow and change position, while maintaining the
basic integrity of the membrane. Both phospholipid molecules and embedded proteins
are able to diffuse rapidly and laterally in the membrane. The fluidity of the plasma
membrane is necessary for the activities of certain enzymes and transport molecules
within the membrane. Plasma membranes range from 5–10 nm thick. As a comparison,

human red blood cells, visible via light microscopy, are approximately 8 µm thick, or
approximately 1,000 times thicker than a plasma membrane.
Figure: The fluid mosaic model of the plasma membrane structure describes the plasma
membrane as a fluid combination of phospholipids, cholesterol, proteins, and
carbohydrates.
The plasma membrane is made up primarily of a bilayer of phospholipids with
embedded proteins, carbohydrates, glycolipids, and glycoproteins, and, in animal cells,
cholesterol. The amount of cholesterol in animal plasma membranes regulates the
fluidity of the membrane and changes based on the temperature of the cell’s
environment. In other words, cholesterol acts as antifreeze in the cell membrane and is
more abundant in animals that live in cold climates.
The main fabric of the membrane is composed of two layers of phospholipid molecules,
and the polar ends of these molecules (which look like a collection of balls in an artist’s
rendition of the model) are in contact with aqueous fluid both inside and outside the
cell. Thus, both surfaces of the plasma membrane are hydrophilic. In contrast, the
interior of the membrane, between its two surfaces, is a hydrophobic or nonpolar region
because of the fatty acid tails. This region has no attraction for water or other polar
molecules.

Figure: This phospholipid molecule is composed of a hydrophilic head and two
hydrophobic tails. The hydrophilic head group consists of a phosphate-containing group
attached to a glycerol molecule. The hydrophobic tails, each containing either a
saturated or an unsaturated fatty acid, are long hydrocarbon chains.
Proteins make up the second major chemical component of plasma membranes. Integral
proteins are embedded in the plasma membrane and may span all or part of the
membrane. Integral proteins may serve as channels or pumps to move materials into or
out of the cell. Peripheral proteins are found on the exterior or interior surfaces of
membranes, attached either to integral proteins or to phospholipid molecules. Both
integral and peripheral proteins may serve as enzymes, as structural attachments for the
fibers of the cytoskeleton, or as part of the cell’s recognition sites.
Carbohydrates are the third major component of plasma membranes. They are always
found on the exterior surface of cells and are bound either to proteins (forming
glycoproteins) or to lipids (forming glycolipids). These carbohydrate chains may consist
of 2–60 monosaccharide units and may be either straight or branched. Along with
peripheral proteins, carbohydrates form specialized sites on the cell surface that allow
cells to recognize each other.
Evolution in Action
How Viruses Infect Specific Organs Specific glycoprotein molecules exposed on the
surface of the cell membranes of host cells are exploited by many viruses to infect
specific organs. For example, HIV is able to penetrate the plasma membranes of specific
kinds of white blood cells called T-helper cells and monocytes, as well as some cells of
the central nervous system. The hepatitis virus attacks only liver cells.
These viruses are able to invade these cells, because the cells have binding sites on their
surfaces that the viruses have exploited with equally specific glycoproteins in their coats.
The cell is tricked by the mimicry of the virus coat molecules, and the virus is able to
enter the cell. Other recognition sites on the virus’s surface interact with the human
immune system, prompting the body to produce antibodies. Antibodies are made in
response to the antigens (or proteins associated with invasive pathogens). These same
sites serve as places for antibodies to attach, and either destroy or inhibit the activity of
the virus. Unfortunately, these sites on HIV are encoded by genes that change quickly,
making the production of an effective vaccine against the virus very difficult. The virus
population within an infected individual quickly evolves through mutation into different
populations, or variants, distinguished by differences in these recognition sites. This
rapid change of viral surface markers decreases the effectiveness of the person’s
immune system in attacking the virus, because the antibodies will not recognize the new
variations of the surface patterns.

Figure 3.23 HIV docks at and binds to the CD4 receptor, a glycoprotein on the surface of
T cells, before entering, or infecting, the cell. (Credit: modification of work by US
National Institutes of Health/National Institute of Allergy and Infectious Diseases)
Section Summary
The modern understanding of the plasma membrane is referred to as the fluid mosaic
model. The plasma membrane is composed of a bilayer of phospholipids, with their
hydrophobic, fatty acid tails in contact with each other. The landscape of the membrane
is studded with proteins, some of which span the membrane. Some of these proteins
serve to transport materials into or out of the cell. Carbohydrates are attached to some
of the proteins and lipids on the outward-facing surface of the membrane. These form
complexes that function to identify the cell to other cells. The fluid nature of the
membrane owes itself to the configuration of the fatty acid tails, the presence of
cholesterol embedded in the membrane (in animal cells), and the mosaic nature of the
proteins and protein-carbohydrate complexes, which are not firmly fixed in place.
Plasma membranes enclose the borders of cells, but rather than being a static bag, they
are dynamic and constantly in flux
Transport across cell membrane
Cells are separated from their surrounding environment by plasma membrane. In
addition, the eukaryotic cells are compartmentalized by intracellular membranes that
form the boundaries and internal structures of various organelles. These biological
membranes are semi-permeable in nature that is their permeability properties ensure
that the specific molecules and ions readily enter the cell and the waste products leave

the cell. These movements of solutes into the cell are mediated through the action of
specific transport proteins that are present on the cell membrane. Such proteins are
therefore required for movements of ions, such as Na+
, K+
, Ca2+
, and Cl-
, as well as
metabolites such as pyruvate, amino acids, sugars, and nucleotides, and even water.
Transport proteins are also responsible for biological electrochemical phenomena such
as neurotransmission.
Cell membrane architecture in transport across cell membrane:
The cell membrane plays an important role in transport of molecules. Because it acts as a
semi-permeable barrier, allowing specific molecules to cross while fencing the majority
of organically produced chemicals inside the cell. Electron microscopic examinations of
cell membranes reveal the development of the lipid bilayer model (fluid-mosaic model).
The model consists of phospholipid, which has a polar (hydrophilic) head and two non-
polar (hydrophobic) tails. These phospholipids are aligned tail to tail so the non-polar
areas form a hydrophobic region between the hydrophilic heads on the inner and outer
surfaces of the membrane.
Permeability of molecules across phospholipid bilayer:
Most of the molecule will diffuse across a protein-free lipid bilayer down its
concentration gradient, if provided enough time. The diffusion rate is the function of the
size of the molecule and its relative solubility in oil. In general, the smaller the molecule
and the more soluble in oil (the more hydrophobic or non-polar), the more rapidly it will
diffuse across a cell membrane. Small non-polar molecules, such as O2 and CO2, readily
dissolve in cell membrane and therefore diffuse rapidly across them whereas small
uncharged polar molecules, such as water or urea, also diffuse across a bilayer, but much
more slowly but ethanol diffuses readily. Conclusively it can be said that lipid bilayers are
highly impermeable to charged molecules (ions) by considering its size also because the
charge and high degree of hydration of such molecules prevents them from entering the
hydrocarbon phase of the bilayer. Thus, these bilayers are 109
times more permeable to
water than to even such small ions as Na+
or K+

Types of transport process:
Two types of transport process occur across the membrane.
1. Non-mediated transport
2. Mediated transport
Non-mediated transport occurs through the simple diffusion process and the driving
force for the transport of a substance through a medium depends on its chemical
potential gradient. Whereas mediated transport requires specific carrier proteins. Thus,
the substance diffuses in the direction that eliminates its concentration gradient; at a
rate proportional to the magnitude of this gradient and also depends on its solubility in
the membrane’s non-polar core. Mediated transport is classified into two categories
depending on the thermodynamics of the system:
1. Passive-mediated transport, or facilitated diffusion: In this type of process a specific
molecule flows from high concentration to low concentration.
2. Active transport: In this type of process a specific molecule is transported from low
concentration to high concentration, that is, against its concentration gradient. Such an
endergonic process must be coupled to a sufficiently exergonic process to make it
favorable (ΔG < 0).
Figure: Mediated transport. (A) Passive transport and (B) Active transport
Passive mediated transport:
Substances that are too large or polar diffuse across the lipid bilayer on their own
through membrane proteins called carriers, permeases, channels and transporters.
Unlike active transport, this process does not involve chemical energy. So the passive
mediated transport is totally dependent upon the permeability nature of cell membrane,

which in turn, is function of organization and characteristics of membrane lipids and
proteins.
Types of passive transport:
1. Diffusion:The process of the net movement of solutes from a region of high
concentration to a region of low concentration is known as diffusion. The differences of
concentration between the two regions are termed as concentration gradient and the
diffusion continues till the gradient has been vanished. Diffusion occurs down the
concentration gradient.
Figure: Diffusion. Extracellular space contains high concentration of solutes than
intracellular space and hence the solutes move from extracellular space to intracellular
space till there is no concentration gradient between the spaces.
2. Facilated diffusion:The process of the movement of molecules across the cell
membrane via special transport proteins that are embedded within the cellular
membrane is known as facilitated diffusion or called carrier-mediated diffusion. Many
large molecules, such as glucose, are insoluble in lipids and too large to fit into the
porins, therefore, it will bind with its specific carrier proteins, and the complex will then
be bonded to a receptor site and moved through the cellular membrane.

Figure: Facilitated transport. Movement of the solutes from extracellular space to
intracellular space via carrier proteins and down its concentration gradient.
3. Filtration: Filtration is the process of the movement of water and solute molecules
across the cell membrane due to hydrostatic pressure generated by the system.
Depending on the size of the membrane pores, only solutes of a certain size may pass
through it. The membrane pores of the Bowman's capsule in the kidneys are very small,
and only albumins (smallest of the proteins) can filter through. On the other hand, the
membrane pores of liver cells are extremely large, to allow a variety of solutes to pass
through and be metabolized.
Figure: Filtration
4.Osmosis: Osmosis is the type of diffusion of water molecules across a semi- permeable
membrane, from a solution of high water potential to a region of low water potential. A
cell with a less negative water potential will draw in water but this depends on other
factors as well such as solute potential (pressure in the cell e.g. solute molecules) and
pressure potential (external pressure e.g. cell wall).
Figure: Osmosis. (A) In hypertonic solution, there are more solute molecules outside the
cell, which causes the water to be sucked in that direction which leads to the shrinkage
of cells. (B) In isotonic solution, there is equal concentration of solute on both sides,
henceforth the water with move back in forth. (C) In hypotonic solution, there are less

solute molecules outside the cell, since salt sucks and water will move inside the cell. The
cell will gain water and grow larger, and finally burst.
Active transport:
Active transport is the movement of a substance against its concentration gradient (i.e.
from low to high concentration). It is an endergonic process that, in most cases, is
coupled to the hydrolysis of ATP.
Types of active transport:
1. Primary active transport: Primary active transport, also called direct active transport,
directly uses energy to transport molecules across a membrane. Example: Sodium-
potassium pump, which helps to maintain the cell potential.
Figure 7: Primary active transport. The action of the sodium-potassium pump is an
example of primary active transport.
2. Secondary active transport: Secondary active transport or co-transport, also uses
energy to transport molecules acr`-oss a membrane; however, in contrast to primary
active transport, there is no direct coupling of ATP; instead, the electrochemical
potential difference created by pumping ions out of the cell is instrumental.

Figure: Secondary active transport
The two main forms of active transport are antiport and symport.
1. Antiport:
In antiport two species of ion or solutes are pumped in opposite directions across a
membrane. One of these species is allowed to flow from high to low concentration
which yields the entropic energy to drive the transport of the other solute from a low
concentration region to a high one. Example: the sodium-calcium exchanger or
antiporter, which allows three sodium ions into the cell to transport one calcium out.
2. Symport:
Symport uses the downhill movement of one solute species from high to low
concentration to move another molecule uphill from low concentration to high
concentration (against its electrochemical gradient).
Example: glucose symporter SGLT1, which co-transports one glucose (or galactose)
molecule into the cell for every two sodium ions it imports into the cell.
(B)Ion Gradient–Driven Active Transport
For example, cells of the intestinal epithelium take up dietary glucose by Na+
-dependent
symport. This process is an example of secondary active transport because Na+
gradient
in these cells is maintained by the (Na+
– K+
)–ATPase.The Na+
– glucose transport system
concentrates glucose inside the cell. Glucose is then transported into the capillaries
through a passive-mediated glucose uniport (which resembles GLUT1).

Figure 10: Glucose transport across Interstinal epithelium. The brushlike villi lining the
small interstine greatly increases the surface area (a), thereby facilating the absorption
of the nutrients. The brush border cells from which the villi are formed (b) concentrate
glucose from the interstinal lumen in symport to Na+
(c), a process that is driven by
(Na+
– K+
) – ATPase, which is located on the capillary side of the cell and functions to
maintain a low internal [Na+
]. The glucose is exported to the bloodstream via a passive-
mediated uniprot system similar to GLUT1.
Bulk transport across cell membrane
In addition to moving small ions and molecules through the membrane, cells also need
to remove and take in larger molecules and particles (see Table for examples). Some
cells are even capable of engulfing entire unicellular microorganisms. You might have
correctly hypothesized that the uptake and release of large particles by the cell requires
energy. A large particle, however, cannot pass through the membrane, even with energy
supplied by the cell.
Endocytosis: Endocytosis is a type of active transport that moves particles, such as large
molecules, parts of cells, and even whole cells, into a cell. There are different variations
of endocytosis, but all share a common characteristic: The plasma membrane of the cell
invaginates, forming a pocket around the target particle. The pocket pinches off,
resulting in the particle being contained in a newly created intracellular vesicle formed
from the plasma membrane.
Phagocytosis: Phagocytosis (the condition of “cell eating”) is the process by which
large particles, such as cells or relatively large particles, are taken in by a cell. For
example, when microorganisms invade the human body, a type of white blood cell
called a neutrophil will remove the invaders through this process, surrounding and
engulfing the microorganism, which is then destroyed by the neutrophil (Figure).

In phagocytosis, the cell membrane surrounds the particle and engulfs it. (Credit:
Mariana Ruiz Villareal)
In preparation for phagocytosis, a portion of the inward-facing surface of the plasma
membrane becomes coated with a protein called clathrin, which stabilizes this section of
the membrane. The coated portion of the membrane then extends from the body of the
cell and surrounds the particle, eventually enclosing it. Once the vesicle containing the
particle is enclosed within the cell, the clathrin disengages from the membrane and the
vesicle merges with a lysosome for the breakdown of the material in the newly formed
compartment (endosome). When accessible nutrients from the degradation of the
vesicular contents have been extracted, the newly formed endosome merges with the
plasma membrane and releases its contents into the extracellular fluid. The endosomal
membrane again becomes part of the plasma membrane.
Pinocytosis:A variation of endocytosis is called pinocytosis. This literally means “cell
drinking” and was named at a time when the assumption was that the cell was
purposefully taking in extracellular fluid. In reality, this is a process that takes in
molecules, including water, which the cell needs from the extracellular fluid.
Pinocytosis results in a much smaller vesicle than does phagocytosis, and the vesicle
does not need to merge with a lysosome (Figure).

In
pinocytosis, the cell membrane invaginates, surrounds a small volume of fluid, and
pinches off. (credit: Mariana Ruiz Villareal)
A variation of pinocytosis is called potocytosis. This process uses a coating protein,
called caveolin, on the cytoplasmic side of the plasma membrane, which performs a
similar function to clathrin. The cavities in the plasma membrane that form the vacuoles
have membrane receptors and lipid rafts in addition to caveolin. The vacuoles or vesicles
formed in caveolae (singular caveola) are smaller than those in pinocytosis. Potocytosis
is used to bring small molecules into the cell and to transport these molecules through
the cell for their release on the other side of the cell, a process called transcytosis.
Receptor-mediated Endocytosis:A targeted variation of endocytosis employs receptor
proteins in the plasma membrane that have a specific binding affinity for certain
substances (Figure).
In receptor-mediated endocytosis, uptake of substances by the cell is targeted to a
single type of substance that binds to the receptor on the external surface of the cell
membrane. (credit: modification of work by Mariana Ruiz Villareal)

In receptor-mediated endocytosis, as in phagocytosis, clathrin is attached to the
cytoplasmic side of the plasma membrane. If uptake of a compound is dependent on
receptor-mediated endocytosis and the process is ineffective, the material will not be
removed from the tissue fluids or blood. Instead, it will stay in those fluids and increase
in concentration. Some human diseases are caused by the failure of receptor-mediated
endocytosis. For example, the form of cholesterol termed low-density lipoprotein or LDL
(also referred to as “bad” cholesterol) is removed from the blood by receptor-mediated
endocytosis. In the human genetic disease familial hypercholesterolemia, the LDL
receptors are defective or missing entirely. People with this condition have life-
threatening levels of cholesterol in their blood, because their cells cannot clear LDL
particles from their blood.
Although receptor-mediated endocytosis is designed to bring specific substances that
are normally found in the extracellular fluid into the cell, other substances may gain
entry into the cell at the same site. Flu viruses, diphtheria, and cholera toxin all have sites
that cross-react with normal receptor-binding sites and gain entry into cells.
Exocytosis
The reverse process of moving material into a cell is the process of
exocytosis. Exocytosis is the opposite of the processes discussed above in that its
purpose is to expel material from the cell into the extracellular fluid. Waste material is
enveloped in a membrane and fuses with the interior of the plasma membrane. This
fusion opens the membranous envelope on the exterior of the cell, and the waste
material is expelled into the extracellular space (Figure). Other examples of cells
releasing molecules via exocytosis include the secretion of proteins of the extracellular
matrix and secretion of neurotransmitters into the synaptic cleft by synaptic vesicles.

In exocytosis, vesicles containing substances fuse with the plasma membrane. The
contents are then released to the exterior of the cell. (Credit: modification of work by
Mariana Ruiz Villareal)
Section Summary
Active transport methods require the direct use of ATP to fuel the transport. Large
particles, such as macromolecules, parts of cells, or whole cells, can be engulfed by other
cells in a process called phagocytosis. In phagocytosis, a portion of the membrane
invaginates and flows around the particle, eventually pinching off and leaving the
particle entirely enclosed by an envelope of plasma membrane. Vesicle contents are
broken down by the cell, with the particles either used as food or dispatched.
Pinocytosis is a similar process on a smaller scale. The plasma membrane invaginates and
pinches off, producing a small envelope of fluid from outside the cell. Pinocytosis
imports substances that the cell needs from the extracellular fluid. The cell expels waste
in a similar but reverse manner: it pushes a membranous vacuole to the plasma
membrane, allowing the vacuole to fuse with the membrane and incorporate itself into
the membrane structure, releasing its contents to the exterior.
Methods of Transport, Energy Requirements, and Types of Material Transported
Transport Method Active/Passive Material Transported
Diffusion Passive Small-molecular weight material
Osmosis Passive Water
Facilitated transport/diffusion Passive Sodium, potassium, calcium, glucose
Primary active transport Active Sodium, potassium, calcium
Secondary active transport Active Amino acids, lactose
Phagocytosis Active
Large macromolecules, whole cells, or cellular
structures
Pinocytosis Active Small molecules (liquids/water)
Receptor-mediated endocytosis Active Large quantities of macromolecules

References:
1. Baldwin, S. A., J. C. Gorga, and G. E. Lienhard (1981); The monosaccharide transporter of
the human erythrocyte. Transport activity upon reconstitution, J. Biol. Chem. 256:3685-
3689.
2. Donald Voet, Judith G. Voet, Charlotte W. Pratt (2008); Fundamentals of Biochemistry-
Life at the Molecular Level: Chapter 10 Membrane transport, 3rd Edition
3. Joyce J. Diwan (1998-2007); Membrane transport,
http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/carriers.htm
4. M. Lodish (2003), Molecular cell biology: Chapter 3 Biomembranes and cell architecture,
5th edition
5. M. Lodish (2003); Molecular cell biology: Chapter 7 Transport of ions and small molecules
across cell membranes, 5th edition
6. Sui H, han BG, Lee JK, Walian P, Jap Bk. (2001); Structural basis of water-specific
transport through the AQP1 water channel, Nature 414:872-878
7. www.Lumenbiology.com

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