BIO 3520 Notes, 8/20/08
PHYSIOLOGY OF THE CELL MEMBRANE
I. Cell Structure and Chemistry. [Widmaier, pg. 24]
A. Chemical composition of the body.
1. Body of a terrestrial animal is 75% water.
2. The remainder is mostly organic compounds.
3. Macromolecules contribute to the structure and function of the cell.
a. Carbohydrates, lipids, nucleic acids, and proteins
(review Widmaier, chapter 2).
1. Essential to life.
2. Polar -- electrons are distributed unevenly between oxygen and two
hydrogen atoms (fig. 2-4).
3. Properties of water.
a. Excellent solvent.
b. Melting point and boiling point compatibility.
c. High heat of vaporization.
d. High surface tension.
4. Water takes part in many reactions.
a. Hydrolysis = Breaking of a covalent bond by the addition of water.
R1 - R2 + H2O > R1 - OH + R2 - H
Ex. hydrolysis of complex carbohydrates to simple sugars.
C. Cell structure.
1. Review major organelles of the cell (pp. 43-55; fig. 3-4).
II. Introduction to the Cell Membrane. [Widmaier, pg. 45]
A. Cell membrane (plasma membrane) separates the intracellular fluid from
the extracellular fluid.
B. Cell membrane is selectively permeable.
III. Structure of the Cell Membrane [pp. 45-48]
(figurea).
A. Membrane lipids.
1. Phospholipids.
a. Forms bilayer due to amphipathic properties (fig. 3-6).
b. Phosphatidylcholine is the most abundant membrane phospholipid
(fig. 2-11).
2. Cholesterol (fig. 2-12).
a. Steroid.
b. Gives membrane stability.
B. Membrane proteins.
1. Integral proteins (fig. 3-7).
a. Located within the lipid bilayer.
b. Most span thickness of membrane.
c. Amphipathic.
d. Functions.
1. Channels.
2. Carriers.
3. Receptors.
2. Peripheral proteins.
a. Located on inner surface of membrane.
b. Polar.
c. Attached to integral proteins.
d. Function -- enzymes.
3. Distribution of proteins makes membrane asymmetrical.
4. Protein binding sites.
a. Sites on protein that can bind selectively and noncovalently to
other molecules.
b. Ligand = Molecule that binds to protein binding site.
c. Binding force is ionic bonds or van der Waals forces (fig. 3-27).
d. Binding is reversible.
L + R <
> L - R complex
e. Characteristics of protein binding sites.
1. Specificity.
2. Affinity.
3. Competition.
4. Saturation (fig. 3-30).
C. Membrane carbohydrates.
1. Attached to proteins and lipids (glycoproteins and glycolipids).
2. Mostly found on outer surface of cell membrane.
3. Serve as cell surface recognition sites (ex. antigens on surface of
red blood cells).
D. Constant rearrangement of protein and phospholipid molecules within
each layer -- fluid-mosaic model (fig. 3-9, figurea).
a Sherwood, L. Human Physiology: From Cells to Systems, 5th ed., Brooks/Cole,
Belmont, CA, 2004. Copyright restrictions apply.
IV. Junctions Between Cells. [pg. 48]
A. Cell membranes are the sites of interaction between adjacent cells.
B. Specialized membrane junctions (fig. 3-10).
1. Desmosomes.
a. Dense accumulation of matter between two membranes.
b. Found in tissues undergoing considerable stretching
(ex. cardiac muscle, skin).
2. Tight junctions.
a. Outer surfaces of two membranes fuse together.
b. Prevent passage of molecules in between cells.
c. Found in epithelial cell layers.
3. Gap junctions.
a. Small channels connecting two cells, allowing direct contact between
their cytoplasm.
b. Allow direct transmission of electrical signals between adjacent cells.
c. Found in cardiac and smooth muscle.
A. Definition:
B. Obeys the Second Law of Thermodynamics.
C. Rate of diffusion limits the size of the cell.
1. Cell diameters range from 2 to 120 µm.
2. Oxygen must be able to diffuse to all parts of the cell.
D. Diffusion across the cell membrane.
1. Model: Phospholipid bilayer (figureb).
2. Flux = Amount of substance crossing a surface per unit time.
a. Bidirectional.
b. Net flux = Difference between the inward and outward fluxes.
c. At equilibrium, net flux = 0.
3. Factors affecting diffusion across membrane.
a. General principle: Flow = Driving force
Resistance
b. Fick's law:
F = P A (Co - Ci)
where F = net flux (moles/sec)
P = permeability coefficient
A = surface area
Co - Ci = concentration gradient
c. Permeability coefficient is increased by:
1. Increased lipid solubility (oil:water partition coefficient) (figurec).
2. Decreased molecular size.
b Moffett, D.F., Moffett, S.B., and Schauf, C.L. Human Physiology: Foundations & Frontiers,
2nd ed., Mosby, St. Louis, MO, 1993. Copyright restrictions apply.
c Randall, D., Burggren, W., and French, K. Eckert Animal Physiology: Mechanisms and
Adaptations, 5th ed., W.H. Freeman, New York, 2002. Copyright restrictions apply.
A. Diffusion of water.
1. High H2O conc.
> low H2O conc.2. Low solute conc.
> high solute conc.
B. Osmolarity = Molar concentration of solutes in a solution.
1. One osmole/l = one mole solute per liter.
a. 1 M glucose = ___ osmol / liter.
b. 1 M NaCl = ___ osmol / liter.
C. Osmotic pressure.
1. If membrane is impermeable to a solute (ex. sucrose), but permeable
to water
>
2. If volume is fixed
>
3. Measurement of osmotic pressure.
4. Osmotic pressure = Pressure that is required to prevent the osmotic
movement of water.
5. Osmotic pressure exerted by a solution is proportional to its
osmolarity (ex. 15% sucrose would not rise as high as 30% sucrose).
6. Importance in physiology.
a. Cell volume.
b. Renal function.
c. Capillaries.
D. Osmosis and hemolysis of red blood cells.
1. Permeability of the RBC membrane to water.
a. Water is a small, polar molecule.
b. Crosses membranes through protein channels called aquaporins.
c. Aquaporins are abundant in RBC membrane.
2. Normal RBC solute conc = 0.3 osmol / liter.
3. Place RBC in a solution with 0.3 osmol/l of solutes that cannot cross
cell membrane (what concentration of NaCl would this be?).
a. Result:
b. This is called an isotonic solution.
4. Place RBC in a solution with less than 0.3 osmol/l of nonpenetrating
solutes (ex. 0.05 M NaCl).
a. Result:
b. This is called a hypotonic solution (figured).
5. Place RBC in a solution with more than 0.3 osmol/l of nonpenetrating
solutes (ex. 0.45 M NaCl).
a. Result:
b. This is called a hypertonic solution.
6. Summary (fig. 4-19 and table 4-3).
7. If a solute can cross cell membrane (ex. MeOH), a 0.3 osmolar solution
can be hypotonic. Explain.
8. Hemolysis of RBC experiment.
RBC Condition
Intact
Hemolyzed
Appearance
Microscope
Centrifuge
9. Diffusion of solutes across RBC membrane.
a. Use hemolysis time to estimate the rate of diffusion of solute
across RBC membrane.
b. Effect of molecular size and polarity.
d Wistreich, G.A. Laboratory Manual for Human Physiology, 1986. Copyright restrictions
apply.
VI. Diffusion of Ions. [pp. 100-101, 144-148]
A. Because of their electrical charge, ions must pass through pores or
channels in the membrane.
1. Composed of integral proteins (fig. 4-7).
2. Channel is filled with water.
3. Entrance to channel is ion selective.
a. Channels are in a dynamic state of opening and closing every few
msec.
C. Factors governing the diffusion of ions across the membrane.
1. Permeability.
a. Cell membrane is very permeable to K+.
b. Less permeable to Cl-.
c. Almost impermeable to Na+.
a. Uneven distribution of ions across cell membrane (table 6-2).
Ion
ECF conc
(mmol/L)
ICF conc
(mmol/L)
ECF/ICF
Na+
K+
Cl-
3. Distribution of electrical charge.
a. Electrical attraction can be used to do work (fig. 6-7).
1. Separated charges have potential energy (electrical potential
difference).
2. Measured in volts or millivolts (mV).
b. All living cells have an unequal distribution of charge across their
cell membranes (fig. 6-8, 6-9).
c. Membrane potential = Electrical potential difference across the
cell membrane.
1. Typical membrane potential is -70 mV (fig. 6-8).
d. Diffusion of ions across a membrane.
1. Case 1: If membrane is permeable to all ions.
2. Case 2: If membrane is permeable to K+, but not permeable
to other ions.
e. Electrochemical equilibrium.
1. Every ion that can cross the cell membrane will distribute
according to its electrochemical equilibrium.
2. Electrochemical equilibrium occurs when the chemical
forces (concentration gradient) balance the opposing
electrical forces (charge gradient).
3. Net flux = 0.
4. Co does not equal Ci.
f. Nernst equation.
1. Used to predict the membrane potential at which an ion is in
equilibrium across the cell membrane.
2. The equilibrium potential for each diffusible ion is the
membrane potential at which the electrical force is equal to
the opposing chemical force.
3. Derivation of the Nernst equation:
4. Examples.
a. ENa =
b. EK =
c. ECl =
g. When membrane potential is -70 mV (fig. 6-12):
1. Cl- is in equilibrium.
2. K+ is nearly in equilibrium.
3. Na+ is out of equilibrium.
a. What prevents Na+ from reaching equilibrium?
VII. Mediated Transport Systems. [pp. 102-107]
A. Large, polar molecules pass through the cell membrane by mediated
transport involving protein carriers (transporters).
B. Facilitated diffusion.
1. Characteristics.
a. Transport along concentration gradient.
b. Uses no metabolic energy.
c. At equilibrium concentrations are equal on both sides.
2. Process (fig. 4-8).
a. Binding to membrane protein (carrier).
b. Carrier changes shape
> transports solute to opposite sideof membrane.
c. Solute dissociates from carrier.
3. Example: Glucose uptake by most cells.
C. Primary active transport.
1. Characteristics.
a. Transport against concentration gradient.
b. Requires metabolic energy.
c. At steady state, concentration is higher in direction transported.
2. Process (fig. 4-11).
a. Binding to membrane protein (carrier or pump).
b. Energy is transferred from ATP.
c. Carrier changes shape
> transports solute to opposite sideof membrane.
d. Solute dissociates from carrier.
3. All known active transport carriers transport ions.
4. Best known -- sodium-potassium pump (fig. 4-12).
a. Pumps K+ into and Na+ out of cells.
b. Energy is derived from ATP.
D. Secondary active transport.
1. Characteristics.
a. Transport against concentration gradient.
b. Transport is indirectly linked to the primary active transport of an ion.
c. Energy comes ultimately from Na-K pump.
2. Process (fig. 4-13).
E. Summary (table 4-2).
VIII. Exocytosis and Endocytosis. [pp. 112-114]
(fig. 4-20)
A. Important for transport of very large molecules across cell membrane.
B. Exocytosis (figuree).
1. Molecules are packaged into membrane-bound secretory vesicles.
2. Move to cell membrane where membranes fuse, releasing contents
outside of cell.
3. Example: Secretion of peptide hormones.
C. Endocytosis (figuree).
1. Molecules or particles bind to outer surface of cell.
2. Cell membrane invaginates around bound particles.
3. Pinches off, moving vesicle inside of cell.
4. Broken down by lysosomes, releasing contents into cytoplasm.
5. Example: Uptake of LDL cholesterol by cells.
e Fox, S.I. Human Physiology, 7th ed., McGraw-Hill, New York, 2002. Copyright
restrictions apply.
IX. Example of Various Transport Systems: Intestinal Epithelial Cell.
[pp. 114-115]
A. Anatomy.
1. Inner surface of intestine is covered with a single layer of epithelial cells.
2. Substances cannot diffuse between the cells due to ______________
junctions.
3. Nutrients are absorbed from the lumen of the intestine across the
epithelial cells into the blood.
4. Two membranes must be crossed (luminal side and blood side).
B. Transport mechanisms involved in absorption of glucose from small
intestine.
1. Na+ is transported against a conc. gradient from cytoplasm to
extracellular space in exchange for K+ (fig. 4-22).
Name of this process:
2. Na+ also passes through protein channels from lumen to cytoplasm
along a conc. gradient (fig. 4-22).
Name of this process:
3. Na+ transport into cell across luminal membrane is linked with
glucose transport against a conc. gradient (fig. 4-23, X = glucose).
Name of this process:
4. Glucose is transported by a protein carrier from cytoplasm to
extracellular fluid along a conc. gradient (in fig. 4-23).
Name of this process:
X. Membrane Receptors. [pp. 120-130]
A. Integral membrane proteins (fig. 5-1).
B. Bind reversibly to chemical messengers (ligands) to produce a
response.
C. Mechanisms of receptor action (signal transduction).
1. Regulation of membrane channels.
a. Opening of ligand-gated ion channels
> increase diffusionof specific ions across the membrane (fig. 5-5a).
2. Second messengers = Intracellular molecules that carry a signal
from the cell membrane to the interior of the cell.
a. Ligand binds to membrane receptor.
b. Causes the formation of a substance on the cytoplasmic side of the
membrane -- second messenger.
c. Second messengers initiate biochemical changes inside the cell
(ex. activation of specific enzymes).
3. Example of a second messenger: Cyclic AMP (fig. 5-6).
a. Binds to receptors on cell membrane.
b. Coupled via a membrane G protein with an enzyme, adenylyl
cyclase, located on the inner surface of the membrane.
c. Adenylyl cyclase is activated.
d. Causes conversion of ATP to cyclic AMP.
e. Cyclic AMP (second messenger) initiates biochemical changes
inside cell, leading to cellular response.
4. Example of a second messenger: Calcium ion.
a. Ligand binds to membrane receptor (fig. 5-11).
b. Opens ligand-gated Ca++ channels in cell membrane.
c. Ca++ enters cell
> increases cytoplasmic Ca++.
d. Ca++ initiates response of cell (ex. contraction of smooth muscle).
XI. Summary.
A. Cell membrane is a selectively permeable phospholipid bilayer.
B. Membrane proteins serve as channels, carriers, and receptors for
interaction with the extracellular environment, or enzymes to catalyze
reactions within the cell.
