Biol 2305
Cell Membrane Structure and Function
Membrane Function
Physical isolation
Surrounds the cytoplasm of a cell and physically separates the intracellular components from
the extracellular environment
Regulation of exchange
Controls the exchange of ions, nutrients, wastes, and products between the cell and
extracellular environment
Communication
Contains membrane-bound proteins that enable the cell to recognize and respond to
molecules in the environment
Structural support
Contains membrane-bound proteins that attach to the cytoskeleton, adjacent cells, and the
extracellular matrix (ECM)
Membrane Structure
All animal cells are surrounded by a plasma membrane
Cell membranes are composed of mostly proteins and
lipids with a small amount of carbohydrate
Approximate composition:
Proteins:
Phospholipids:
Cholesterol:
Other lipids:
Carbohydrates:
55%
25%
13%
4%
3%
Ratio of protein to lipid varies depending on metabolic
activity of the cell or organelle
Example: The inner membrane of a
mitochondrion, which is highly metabolic, is 75%
protein
Be able to identify and define:
Phospholipids
Integral Proteins
Transmembrane Proteins
Peripheral Proteins
Glycoproteins
Glycolipids
Cholesterol
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Fluid Mosaic Model
In 1972, S. Singer and G. Nicolson proposed the Fluid Mosaic Model of membrane structure
Membrane Structure – Phospholipid Bilayer
Phospholipid Bilayer
In a phospholipid molecule, two of the –OH (hydroxyl) groups on glycerol are joined to two
fatty acids. The third –OH joins to a phosphate group which joins, in turn, to another polar
group of atoms
Phosphate and polar groups form a hydrophilic, polar head
Hydrocarbon chains of the 2 fatty acids form hydrophobic, nonpolar tails
The phospholipid bilayer is made of two layers of phospholipids
Non-polar, fatty acid tails point inward
Polar heads are on either surface
Polar
hydro-philic
heads
Nonpolar
hydro-phobic
tails
Polar
hydro-philic
heads
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Membrane Structure – Phospholipid Bilayer
Membrane Steroid Cholesterol
In animal cells, cholesterol that is wedged between phospholipid molecules acts as a
“temperature buffer,” resisting changes in membrane fluidity as the temperature changes
At warm temperatures (such as 37°C), cholesterol restrains the movement of
phospholipids and reduces fluidity
At cool temperatures, it maintains fluidity by preventing tight packing
Membrane Components
Membrane Carbohydrates
On the external surface, carbohydrate groups join with lipids to form glycolipids, and with
proteins to form glycoproteins
These carbohydrate groups serve as cell identity markers by interacting with the surface
molecules of other cells, facilitating cell-cell recognition
The layer of glycoproteins and glycolipids form a fuzzy, protective layer known as the
glycocalyx
Cell-cell recognition is a cell’s ability to distinguish one type of neighboring cell from another
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Membrane Proteins
A membrane is a collage of different proteins embedded in the fluid matrix of the lipid bilayer
Integral proteins penetrate the hydrophobic core of the lipid bilayer
Many integral proteins are also transmembrane proteins, spanning the depth of the
membrane, protruding into the cytoplasm and ECF
Peripheral proteins are loosely bound to integral proteins, phospholipid heads, or fatty acid
tails as lipid-anchored proteins
Functions of Cell Membrane Proteins
Transport – Regulate the passage of substance into and out of cells and between cell organelles and
cytosol, as transporters such as channels or carriers
Enzymatic Activity – Catalyze chemical reactions, as membrane-embedded enzymes
Signal Transduction – Binds to an extracellular signal ligand and generates a cellular response
without allowing the ligand into the cell
Cell-cell recognition – Identify with other body cells as self and non-foreign
Intercellular Joining – Link adjacent cells together by membrane junctions
Anchor to the cytoskeleton & ECM – Anchor cells to the intracellular cytoskeleton and extracellular
matrix
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6 Major Functions Of Membrane Proteins
Transport
A protein that spans the membrane (a transmembrane
protein) may provide a hydrophilic channel through the
membrane, allowing other hydrophilic particles to pass
through. Other transport proteins shuttle a substance
from one side to the other by changing shape. Some of
these proteins hydrolyze ATP as an energy source to
actively pump substances across the membrane
Enzymatic activity
A protein built into the membrane may be an enzyme with
its active site exposed to substances in the ICF
(intracellular fluid)
Signal transduction
A membrane protein (cell surface receptor) will have a
binding site with a specific shape that fits a specific
chemical messenger, such as a hormone. The external
messenger (signal) may cause a conformational change in
the protein (receptor) that then relays the message to the
inside of the cell.
Cell-cell recognition
Some glycoproteins and glycolipids serve as identification
tags that are specifically recognized by other cells.
Intercellular joining
Membrane proteins of adjacent cells may hook together in
various kinds of junctions, such as gap junctions or tight junctions
Attachment to the cytoskeleton and extracellular matrix (ECM)
Microfilaments and microtubules of the cytoskeleton, as well as fibers in the ECM such as
fibronectin may be bonded to membrane proteins - a function that helps maintain cell shape and
stabilizes the location of certain membrane proteins
Cell Junctions
Cell junctions - Long-lasting or permanent connections between adjacent
cells, 3 types of cell junctions: Tight, anchoring & communicating.
1. Tight Junctions - Connect cells into sheets. Because these junctions
form a tight seal between cells, in order to cross the sheet, substances
must pass through the cells, they cannot pass between the cells.
2. Anchoring Junctions - Attach the cytoskeleton
of a cell to the matrix surrounding the cell, or to
the cytoskeleton of an adjacent cell.
3. Communicating (Gap) Junctions - Link the
cytoplasms of 2 cells together, permitting the
controlled passage of small molecules or ions between
them.
Two adjacent connexons
form a gap junction
Connexon
Adjacent plasma
membranes
Intercellular space
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Membrane Transport
The plasma membrane is the boundary that separates the living cell from
its nonliving surroundings
In order to survive, a cell must exchange materials with its surroundings, a
process controlled by the plasma membrane.
Materials must enter and leave the cell through the plasma membrane.
Membrane structure results in selective permeability-- it allows some
substances to cross more easily than others
Two types of membrane transport:
Passive
Active
Solutions, Fluids, and Compartments
Solution – homogeneous mixture of two or more components
Solvent – dissolving medium (often water)
Solutes – components in smaller quantities within a solution
Solute + Solvent = Solution
Intracellular fluid (ICF) – nucleoplasm and cytosol
Extracellular fluid (ECF)
Interstitial fluid (ISF) – fluid on the exterior of the cell within
tissues
Plasma – fluid component of blood
Passive Transport
Passive transport is diffusion of a substance across a membrane with no energy (ATP) being used
Diffusion - the net movement of a substance from an area of high concentration to an area of low
concentration; down its concentration gradient
Caused by the constant random motion of all atoms and molecules
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Diffusion Across A Membrane
The membrane has pores large enough for the molecules to pass through.
Random movement of the molecules will cause some to pass through the pores; this will happen more
often on the side with more molecules. The dye diffuses from where it is more concentrated to where it
is less concentrated
This leads to a dynamic equilibrium – the solute molecules continue to cross the membrane, but at
equal rates in both directions.
Two different solutes are separated by a membrane that is permeable to both
Each solute diffuses down its own concentration gradient.
There will be a net diffusion of the purple molecules toward the left, even though the total solute
concentration was initially greater on the left side
The Permeability of the Lipid Bilayer
4 Permeability Factors
Lipid solubility
Size
Charge
Presence of channels and transporters
Hydrophobic (non-polar) molecules are lipid soluble and can pass through the phospholipid
membrane easily
Small molecules pass through much more easily than large molecules
Charged molecules do not cross the membrane as easily as neutral molecules
Transport proteins allow passage of hydrophilic, large, or charged substances across the membrane
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Lipid Solubility and Size
Polar molecules are lipophobic and generally cannot pass through the phospholipid bilayer without a
channel or carrier protein
Fats (lipids) and other nonpolar substances are lipophilic which allows them to diffuse through the
lipid center (fatty acid tails) of the phospholipid bilayer relatively easily
Passive Transport Processes
3 special types of diffusion that involve movement of materials across a semipermeable membrane:
Dialysis - selective diffusion of solutes
Lipid-soluble materials
Small molecules that can pass through membrane pores unassisted
Facilitated diffusion – substances require a protein carrier or channel for passive transport
Osmosis – simple diffusion of water
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Osmosis
Osmosis - the diffusion of water across a semipermeable membrane from an area of low solute
concentration to an area of high solute concentration
In some circumstances, the solvent may be something other than water. However, in living
systems the solvent is always water, so biologists generally define osmosis as the diffusion of
water across a semipermeable membrane.
Osmotic Pressure
Osmotic pressure - the pressure exerted to prevent the inward flow of water across a semipermeable
membrane toward a higher concentration of solutes
Consider osmotic pressure to be the pressure that water exerts against a membrane as it tries
to move toward the higher concentration of solutes
The more solutes on the other side of a membrane  the more pressure water will exert against
the membrane  the higher the osmotic pressure
The osmotic pressure is used to help determine the concentration of a solution
The higher the [solutes] in a solution, the higher its osmotic pressure.
When you place a word in brackets, it means “concentration of”
Example: [Ca2+] = “concentration of calcium ions”
Tonicity - a measure of the osmotic pressure gradient
Hypertonic - having a higher osmotic pressure than…
Hypotonic - having a lower osmotic pressure than…
Isotonic - having the same osmotic pressure as…
Tonicity
If two solutions have an equal [solute], their osmotic pressures are at equilibrium, and they are isotonic
If a solution has a comparatively higher [solute], it is hypertonic
The solution with the comparatively lower [solute] is hypotonic
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Facilitated Diffusion
In Facilitated Diffusion, the diffusion of particles (high to low) across a semipermeable membrane is
facilitated by membrane proteins
i.e. large polar molecules and ions that cannot pass through phospholipid bilayer
In the absence of those membrane proteins, diffusion would not occur
Two types of transport proteins can help ions and large polar molecules diffuse through cell
membranes:
1) Channel proteins – provide a narrow channel for the substance to pass through.
2) Carrier proteins – physically bind to the substance on one side of membrane and release it
on the other
Facilitated Diffusion
Characteristics of Facilitated Diffusion:
Specificity – each channel or carrier transports specific ions or molecules, and nothing else
Passive – the direction of net movement is always down the concentration gradient, no energy
(ATP) is needed
Saturation – once all transport proteins are occupied, the rate of diffusion cannot increase
further, and the transport maximum has been reached
Active Transport
Uses energy from ATP or another particle’s concentration gradient to move a substance against its
concentration gradient
Requires the use of carrier proteins (transport proteins that physically bind to the substance being
transported), not channel proteins
2 types of Active Transport:
Membrane pump (protein-mediated active transport)
Coupled transport (cotransport)
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Membrane Pump
A carrier protein uses energy from ATP to move a substance across a
membrane, up its concentration gradient:
The Na+/K+ Pump
An example of a membrane pump
Pronounced “sodium-potassium pump”
Also called “Na+/K+ ATPase”
Coupled transport
2 proteins involved:
The initial carrier protein uses ATP to move substance 1 across the membrane against its
concentration gradient, storing potential energy.
Coupled transport protein (“cotransporter”) allows substance 1 to move back down its
concentration gradient, using its stored energy to move substance 2 up its concentration
gradient
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Bulk Transport
Bulk Transport allows large particles to enter or leave a cell without actually passing through the
membrane.
2 mechanisms of bulk transport:
Endocytosis
The plasma membrane envelops particles or fluid, then seals on itself to form a vesicle
or vacuole that pinches off into the cell
Phagocytosis – intake of a solid particle
Pinocytosis – intake of a liquid
Exocytosis
Reverse of endocytosis
The membrane of a vesicle fuses with the plasma membrane and its contents are
released outside the cell
Endocytosis (Phagocytosis), Digestion, and Exocytosis
Phagocytosis
The substance engulfed is a solid particle, and encased in a vacuole made of the same phospholipid
bilayer as the cell membrane
Pinocytosis
The substance engulfed is a liquid, and encased in a vacuole made of the same phospholipid bilayer
as the cell membrane
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Exocytosis
Simply the reverse of endocytosis
The membrane of a vesicle fuses with the plasma membrane and its contents are released outside the
cell
Cells Communication
Direct contact
local, cell to cell communication via junctions or direct contact
Paracrine signaling
“para-” = near; “-crine” = secrete
local communication between nearby cells via secretion of cytokines
Synaptic signaling
local secretion of neurotransmitters by a neuron into a synapse with another neuron or other
target cell
Endocrine signaling
“endo-” = within; “-crine” = secrete
also called hormone signaling
long distance communication via secretion of hormones into the bloodstream
Cell Signaling
Chemical signals fall under two categories: Lipophilic
and Lipophobic
Lipophilic ligands – can diffuse through the phospholipid
bilayer of the cell membrane and bind to cytosolic or
nuclear receptors, to generate a response within the cell
Cytosolic receptors can modify gene expression
within the nucleus, or alter existing cytosolic
proteins
Nuclear receptors can turn genes on or off,
regulating protein synthesis
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Lipophobic ligands – are unable to diffuse through the phospholipid bilayer and, instead, bind to
receptor proteins on the membrane, thereby transducing the signal and generating an intracellular
response without entering the cell
Ligand-gated (chemically-gated) ion channels
Enzymatic receptors
G protein-linked receptors
Chemically-Gated Ion Channels
Chemically-Gated Ion Channels open or close when the signal molecule (ligand) binds to the channel
protein
Found on the cell membrane, allowing ions in or out of the cell
Also found on plasma membranes of organelles inside of the cell
Most are neurotransmitter receptors on nerve and muscle cells
Example:
Acetylcholine, a neurotransmitter, is released from a neuron and binds to the acetylcholine
receptors, which opens a channel, allowing Na+ to enter the cell, flowing down its
electrochemical gradient.
Net entry of Na+’s positive charge depolarizes the cell.
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Enzymatic Receptors
Enzyme-linked receptors are embedded in the plasma membrane, with their catalytic site exposed
inside the cell
A signal molecule binds to the receptor site, activating the catalytic site within the cell
Most enzyme-linked receptors function as protein kinases, which are enzymes that phosphorylate
proteins
Phosphorylation is the addition of a phosphate (PO4-3) group to a protein which activates it
The phosphate group is donated by energy molecules such as ATP
Enzymatic Receptors
The most common enzyme-linked receptor is the receptor tyrosine kinase (RTKs)
For example, Receptor Tyrosine-Kinases are used by:
Insulin to initiate the insertion of GLUT4 proteins into the plasma membrane for the facilitated
diffusion of glucose into the cell
Growth factors to spur mitosis and cell division.
Because of its role in cell division, excessive tyrosine kinase signaling is associated with
many types of cancer
Enzymatic Receptors
Protein kinases activate other proteins
Creates a cascade-like pathway eventually leading to a targeted
cellular response
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Signal Transduction through G Proteins
Most Signal Transduction Pathways use G Proteins
Three stages of Signal Transduction:
Reception – each target cell has
membrane receptors that detect a specific
signal molecule and binds to it
Transduction – binding of the signal
molecule changes the receptor protein in
some way that initiates transduction or
conversion of the signal that can be
amplified through a cascade of enzymatic
reactions
Response – the last signal molecule
initiates synthesis of target proteins in the
nucleus or modifies existing proteins in the
cytosol to create a response
Reception: Signal molecule binds to surface
receptor, which activates a G protein
Transduction: G protein activates the membranebound enzyme, adenylyl cyclase, which catalyzes
synthesis of cAMP, which binds to a protein kinase
Response: Target protein initiates cellular change
G Protein-linked Receptors
Signal molecule joins to a receptor, the receptor activates a G protein
The activated G protein can then activate an ion channel or enzyme in the
plasma membrane.
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Second Messengers
Some enzymatic receptors and most G-protein-linked receptors relay their message into the cell by
activating other molecules or ions inside the cell
Convert extracellular signals into intracellular messages which create a response
Second messengers – molecules & ions that transmit the message within the cell
Most common second messengers:
cAMP
Ca2+
cAMP Second Messenger G protein signaling pathway
1. Signal molecule binds to surface receptor
2. Surface receptor activates a G protein
3. G protein activates the membrane-bound enzyme, adenylyl cyclase
4. Adenylyl cyclase catalyzes synthesis of cAMP, which binds to a protein kinase
5. Target protein initiates cellular change
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Cyclic AMP
cAMP recycling takes place in the mitochondria as a part of ATP synthesis
Cyclic AMP Pathway Amplification
Receptor proteins interact with signal molecules at the surface of the cell.
In most cases, the signals are relayed to the cytoplasm or the nucleus by second messengers, which
influence the activity of one or more enzymes or genes inside the cell.
However, most signaling molecules are found in such low concentrations that their effects in the
cytoplasm would be minimal unless the signal was amplified.
Therefore, most enzyme-linked and G protein-linked receptors use a chain of other protein messengers
to amplify the signal as it is being relayed.
In the case of a protein kinase cascade, one cell surface receptor activates many G protein molecules.
Each G protein activates many adenylyl cyclases. Each cyclic AMP in turn will activate protein kinases,
which then activates several molecules of specific enzyme.
The end result is rapid production of high levels of the final product.
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Calcium and IP3 in Signaling Pathways
Signal molecule binds to surface receptor
Surface receptor activates a G protein
G protein activates the membrane-bound enzyme, phospholipase C
Phospholipase C catalyzes synthesis of inositol triphosphate (IP3), which stimulates release of Ca2+
from ER
Released Ca2+ initiates cellular change
Signal Amplification
Stimulation of glycogen breakdown in a liver cell by
epinephrine
Epinephrine binds to G-protein receptor which…
…activates 100 G-proteins which…
…activates 100 adenylyl cyclases ezymes which…
…activates 1000 cyclic AMP molecules which…
…ativates 1000 protein kinase enzymes which…
…activates 100,000 phosphorylase kinase enyzymes
which…
…activates 1,000,000 glycogen phosphorylase
enzymes which…
…convert chains of glycogen into 100,000,000
glucose molecules…
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A Phosphorylation Cascade
A relay molecule activates protein kinase 1.
Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus
activating this second kinase.
Active protein kinase 2 then catalyzes the phosphorylation (and activation) of protein kinase 3.
Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the
signal.
Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the
proteins, making them inactive and available for reuse.
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