Dr.

Ken Lerea
PLASMA MEMBRANE
(see Ross & Pawlina, Histology: A Text & Atlas, 6
th
edition, Ch 2)

Case 1:
A 29 year old patient presents with the following symptoms:

normocytic anemia (decreased hemoglobin content with a normal mean corpuscular volume
(MCV).
Hemoglobinuria (free hemoglobin in the urine)
intravascular hemolysis
leucopenia
thrombocytopenia

PNH (paroxysmal nocturnal hemoglobinuria) is suspected. Flow cytometry is conducted to detect
CD55 and CD59 expression on erythrocytes and the test indicate an absence of these antigens. Which
of the following reasons explain the decreased expression?

i. Altered glycosylation.
ii. Mutations in the gene responsible for synthesis of phosphatidylinositol glycans.
iii. Extended lifetime of erythrocytes.
iv. Inherited mutation in the genes encoding CD55 and CD59
v. Increase secretion of matrix metaloproteases.


Case 2:

A 40-year old was admitted to the emergency room with complaints of dyspnea (shortness of breath)
and leg swelling; ultimately diagnosed with left femoral vein thrombosis and pulmonary embolism.
The patient ultimately acquired mild splenomegaly (enlargement of the spleen) and thrombocytopenia
(decreased platelet numbers). Activities of protein C, protein S, and antithrombin were found to be
normal. Anti-phospholipid antibodies were detected and following other tests the patient was
diagnosed with Antiphospholipid syndrome. You analyzed the topography of the plasma membrane of
platelets and erythrocytes from this patient: What do you expect to find?


NOMENCLATURE:
Plasma membrane, cell membrane, plasmalemma, sarcolemma (muscle)

1. GENERAL FEATURES of PLASMA MEMBRANES
self-forming.
pivotal in: endocytosis/exocytosis, adhesion, movement (chemotaxis), signal transduction.
discriminating selectively permeable barriers controlling movement of nutrients and waste.
surround every cell and specialized apical structures (microvilli, stereocilia, cilia).
contain proteins, lipids, and sugar moieties.
contain molecules that anchor to extracellular matrix and cytoskeletal structures.
asymmetrical with respect to lipid distribution and protein structure.
includes the cell coat (glycocalyx).
Plasma membrane, page 2




























2. PHYSICAL FEATURES- Transverse EM sections (8-10 nm in diameter):



















Fine structure of cells and
tissues. Porter & Bonneville,
eds. Lea & Febiger 3
rd

edition. 1968. P6
Plasma membrane, page 3
3. ARCHITECTURE:
All biological membranes contain lipids and proteins, but their ratio differs.
Basic organization: a phospholipid bilayer with hydrophobic tails facing the interior and the
hydrophilic head groups facing out. Cholesterol and integral membrane proteins make the bilayer
a selectively permeable structure. The plasma membrane is not a rigid structure: Both proteins and
phospholipids diffuse.













4. LIPIDS:
water-insoluble biomolecules.
form the bilayer matrix of membranes.
Form artificial structures (liposomes) in an aqueous solution.
amphipathic.
function in forming membrane structure, cell-cell interactions, signaling.
Major classes found in membranes:

phospholipids glycolipids











cholesterol









Molecular Cell Biology.
Lodish et al. 4
th
edition.
pp158 & 159.
Molecular Cell Biology.
Lodish et al. 4
th
edition. p6.
Chemical Composition of some purified membranes
Membrane Protein Lipid Carbohydrate
Myelin 18% 79% 3%
Plasma membrane 49% 43% 8%
Mitochondrial Inner 76% 24% 0%
membrane
Plasma membrane, page 4
5. PHOSPHOLIPIDS (glycerol-based or sphingosine-based).
compose greater than 50% mass of membranes.
Glycerol-based phospholipids:
sites 1 and 2 bound by fatty acid chains (hydrophobic tails).
fatty acid chains are saturated (no double bonds) or unsaturated (1 or more d.b.).
saturated chains pack tighter, decreasing net fluidity at physiological temperatures.
unsaturated chains increase membrane fluidity and increase membrane leakiness.
Shorter fatty acid chains increase fluidity.
phospholipid nomenclature is derived from the polar head groups:
choline phosphatidylcholine
ethanolamine phosphatidylethanolamine
inositol phosphatidylinositol
serine phosphatidylserine





























Think Box:
1. Is the lateral movement of phospholipids limited?
2. What is a potential consequence if the asymmetry of phospholipids is changed?
3. What is the net charge of phospholipids?
4. List biological functions of lipids.

(i)
(ii)
(iii)
(iv)
(v)
(vi)
(vii)

Molecular Cell Biology.
Lodish et al. 4
th
edition.
p158.
Plasma membrane, page 5
6. STEROLS: Cholesterol
the major steroidal constituent of membranes.
amphipathic.
intercalates between fatty acid chains of phospholipids.
decreases membrane fluidity at physiologic temperatures: restricts motion of fatty acid tails.
increases membrane fluidity at low temperatures: prevents aggregation of fatty acid chains.
together with sphingolipids aggregate forming discrete microdomains known as rafts.

7. GLYCOLIPIDS
amphipathic lipids containing carbohydrate groups.
exclusively found in the outer leaflet.
are minor membrane component
are responsible for ABO blood groups (discussed in blood lecture)
are responsible for uptake of toxins (discussed in Biochemistry)

8. PROTEINS.
asymmetrical and make the bilayer selectively permeable.
Transmembrane proteins- contain one or more hydrophobic segments.
Anchored membrane proteins- contain a consensus sequence motif for modification by
lipid anchors.
C-terminal CAAX motif- isoprenylation (farnesyl; geranyl-geranyl)
N-terminal GXXXS/T motif- myristic acid
N-Terminal cysteine residue- palmitic acid
GPI (glycerophosphatidylinositol)-linked proteins
Peripheral proteins: protein associated with integral membrane proteins or membrane
lipids. Peripheral proteins are easily extracted.
N-lined sugar moieties that face the outside of the cell.
disulfide bridges tend to face the outside of the cell.
function in cell-cell recognition, as receptors, and as transport molecules.














Think Box:
Defects in isoprenylation may affect which of the following?
a. intracellular signaling events.
b. Nuclear structure.
c. Gene expression
d. Aging
Plasma membrane, page 6
9. MEMBRANE FLUIDITY. Factors that control/disrupt fluidity include:
temperature
lipid/fatty acid species
cholesterol
disruption of the cytoskeleton
detergents
anesthetics
hormones (indirectly)


10. SPECIALIZED REGIONS.
apical vs. basolateral
tight junctions
gap junctions
coated pits
caveolae/ lipid rafts
microvilli
cilia


11. SUGARS.
represent stained part of the glycocalyx (20 nm - 0.5 m). Glycocalyx definition: the
oligosaccharides bound to integral and adsorbed plasma membrane glycoproteins,
glycolipids, and proteoglycans.
mediate cell-cell recognition and adhesion (homing of lymphocytes; neutrophil binding;
sperm-egg interactions)
are recognized by sugar recognizing proteins known as lectins.
protect surface from proteolytic damage
maintain the nonthrombogenic surface of endothelial cells. (They repel platelets).
contain and adsorb digestive enzymes
















Molecular Biology of the
Cell. Alberts et al., 3
rd

edition. p 502.
Fine structure of cells and tissues.
Porter & Bonneville, eds. Lea &
Febiger 3
rd
edition. 1968. P30
Plasma membrane, page 7
TRANSPORT SYSTEMS

FUNCTIONS:
regulating cell volume, pH, ionic composition (see Table 1, Plasma membrane page 8).
generating ionic gradients essential for the excitability of nerves and muscle


Transport of ions
Carrier proteins:
passive-transport (facilitated diffusion). down a concentration gradient
active transport.
maintains intracellular concentration of K
+
, Na
+
, Ca
++

maintains membrane potential across the plasma membrane at 70mV
requires energy in the form of:
ATP (e.g., Na/K ATPase)
ion gradients (e.g., co-transport systems; symport, antiport)
Channels: hydrophilic pores allowing solutes to cross membranes passively:
gap junctions & porins. Channels with relatively large permissive pores
Ion channels. displays selectivity (voltage-gated, mechanical, ligand-gated)

Transport of macromolecules:
Endocytosis: pinocytosis vs. receptor-mediated endocytosis
Phagocytosis: engulfment












Think Box:

How does the distribution of transport systems about polarized cells maintain cellular
homeostasis?


What consequence would you expect if a channel, such as the chloride channel in the
lung, is misfolded?
Plasma membrane, page 8

Table 1: Typical ion concentrations in vertebrates













Table 2: Size of cellular structures & resolving power of microscopes:

A. Microscope Resolution
light microscope 0.2 m
electron microscope 2 nm

B. Cellular structure Size
cells 10-100 m
nucleus 3- 10 m
microvilli 1.4 m
mitochondria 0.5 m (width)
lysosomes 0.2-0.5 m
peroxisomes 0.2 - 0.5
Golgi vesicles 50 nm
cytoskeletal elements 8-25 nm
plasma membrane 10 nm





Ions Cell, mM Blood, mM
K
+
140 4
Na
+
12 145
Cl
-
4 105
HC03
-
12 24
Mg
++
0.8 1.5
Ca
++
<0.0005 2