Download Lecture 9 MEMBRANES

Lecture 9
MEMBRANES
Structure & Dynamics
[email protected]
http://glutxi.umassmed.edu/
S1-824 (a.m.), LRB 926 (p.m.)
6-5570
The Cell Membrane
http://www.youtube.com/watch?v=Qqsf_UJcfBc
Objective of Class
•
To emphasize that biomembranes comprise
noncovalent, self-assembling, multicomponent,
dynamic, macromolecular assemblies of
amphipathic molecules.
Specific Goals
This lecture reviews:
•
Biomembranes
•
Lipid Structure
•
Physical Properties of Lipids
•
Physical properties of lipid bilayers
•
Properties & uses of detergents
•
Lipid distribution within and across bilayer
leaflets
(From Bloom and Fawcett, A Textbook of Histology, Chapman and Hall, N.Y., 12th edition, 1994, Figure 1-2.)
Membranes separate the cell from the outside world and separate organelles
inside the cell to compartmentalize important processes and activities.
Cellular membranes have diverse, location-specific functions within the cell. At
the electron microscopic level, membranes share a common structure
following routine preparative steps.
The figure above shows a typical "Unit" membrane which resembles a railroad
track with two dense lines separated by a clear space. This figure was
obtained by cell fixation/sectioning and staining with osmium tetroxide (an
electron opaque agent that binds to a variety of organic compounds). This
figure actually shows two adjacent plasma membranes, both of which have the
"unit membrane" structure.
Membranes can be isolated in several
ways.
•
Red cells are simply a plasma membrane
plus cytosolic proteins - hypotonic lysis of
red cells produces cytoplasm-free
membranes.
•
Other, more complex cells must be
homogenized and membrane fractions
isolated by density centrifugation
(organelle membranes and fragments
have densities distinct from those of
plasma membranes).
Analysis of the composition of isolated
membranes indicates that the major
constituents are:
1. lipids (phospholipids and cholesterol)
2. proteins
3. carbohydrates.
Lipid Structure
H2C
H
C
glycerol
CH2
OH OH OH
OH
O
P
H
O
H2C
OH OH
CH2
OH
glycerol-3-phosphate
Hundreds of different kinds of fatty acids are found. Some have 1 or more double bonds in
their hydrocarbon tail and are called unsaturated. Fatty acids with no double bonds are
saturated.
This double bond is
rigid and creates a
kink in the chain.
The rest of the chain
is free to rotate
about the other C-C
bonds.
In nature most unsaturated fatty acids are cis fatty acids, meaning
the hydrogen atoms are on the same side of the double carbon
bond. In trans fatty acids the two hydrogen atoms are on opposite
sides of the double bond.
Table 11-1
The Common Biological Fatty Acids
Symbol"
Common Name
Saturated fatty acids
12:0
Lauric acid
14:0
Myristic acid
Palmitic acid
16:0
18:0
Stearic acid
Arachidic acid
20:0
22:0
Behenic acid
24:0
Lignoceric acid
Systematic Name
Dodecanoic acid
Tetradecanoic acid
Hexadecanoic acid
Octadecanoic acid
Eicosanoic acid
Docosanoic acid
Tetracosanoic acid
Unsaturated fatty acids (all double bonds are cis)
16:1
Palmitoleic acid
9-Hexadecenoic acid
18:1
Oleic acid
9-0ctadecenoic acid
9,12 -Octadecadienoic acid
Linoleic acid
18:2
9,12,15-0ctadecatrienoic
Q- Linolenic acid
18:3
acid
6,9,12 -Octadecatrienoic
y-Linolenic acid
18:3
acid
5,8,11,14-Eicosatetraenoic
Arachidonic
20:4
acid
acid
5,8,11,14,1720:5
EPA
Eicosapentaenoic acid
15 -Tetracosenoic acid
24:1
Nervonic acid
Structure
CH3(CH2)lOCOOH
CH3(CH2)12COOH
CH3(CH2)14COOH
CH3(CH2)16COOH
CH3(CH2)lSCOOH
CH3(CH 2h oCOOH
CH3(CH2h2COOH
CH3(CH2hCH= CH(CH 2hCOOH
CH3(CH2hCH=CH(CH2)7COOH
CH3(CH2MCH=CHCH2MCH2)6COOH
CH3CH2(CH =CHCH2h(CH2)6COOH
mp ("C)
44.2
52
63.1
69.6
75.4
81
84.2
-0.5
13.4
-9
-17
-49.5
-54
39
• Number of carbon atoms: Number of double bonds.
Source: Dawson, R. M.
Clarendon Press (1969).
c., Elliott, D. c., Elliott, W. H., and Jones, K. M., Data for Biochemical Research (2nd ed.), Chapter 11,
R2
O
O
H2C
O
O
R1
a glycerophospholipid
CH2
H
O
O
P
X
O-
The common Classes of Glycerophospholipids
O
O
H2CH CO O C C R1R
2
1
O O
R2 C CO O CHCH
R2
OO
H2CH2C O OP P OO RR
33
O-ONAME OF R3
Water
Ethanolamine
Choline
Serine
FORMULA OF R3
NAME OF PHOSPHOLIPID
–H
–CH2CH2NH3+
Phosphatidic acid
Phosphatidylethanolamine
–CH2CH2N(CH3)3+
Phosphatidylcholine (lecithin)
–CH2CH(NH3+)COO-
Phosphatidylserine
H
OH
myo-inositol
H
Glycerol
OH
H
OH
OH
H
H
OH
Phosphatidylinositol
H
Phosphatidylglycerol
–CH2CH(OH)CH2OH
O
Phosphatidylglycerol
–CH2CH(OH)CH3
O
P
O
CH2
R4
OHC
O
C O CH2
Diphosphatidylglycerol
(cardiolipin)
O
O
C
R5
CH3
H3C
N+
CH3
CH2
CH2
O
-O
P
O
O
H
H2C
C
CH2
O
O
C
C
ester linkage
O
O
(CH 2)7 (CH2)14
CH
CH3
CH
(CH2)7
CH3
1-Palmitoyl-2-oleoyl-3-phosphatidylcholine
In nature most unsaturated fatty acids are cis fatty acids, meaning
the hydrogen atoms are on the same side of the double carbon
bond. In trans fatty acids the two hydrogen atoms are on opposite
sides of the double bond.
CH3
H3C
N+ CH3
CH2
CH2
O
O
H
O-
O
H2C
O
P
CH2
O
O
C
C
O
(CH2)16 (CH2)16
CH3
CH3
1,2-Distearoyl-3- phosphatidylcholine
Text
Sphingosine
H3C
(H2C)12
C
H
C
H
H2
C
H
C
H
C
OH
NH3+
OH
Sphingomylein
O
H3C (H2C)12
C
H
H3C
C
H
H
C
H
C
OH
NH
(H2C)14
C
H2
C
O
P
O
H2
C
H2
C
N+
CH3
CH3
phosphoryl choline
unit
CH3
O-
amide linkage
O
fatty acid unit
Cerebroside (a glycolipid)
H OH
H3C (H2C)12
C
H
H3C
C
H
H
C
H
C
OH
NH
(H2C)14
C
H2
C
H O
O
H
O
H
OH
fatty acid unit
H
OH
OH
glucose or galactose unit
CH3
HC
CH3
CH3
HO
Cholesterol
CH3
C
H2
C
H2
C CH
H2
CH3
TABLE 10–1 Approximate Lipid Compositions of Different Cell Membranes
PERCENTAGE OF TOTAL LIPID BY WEIGHT
LIPID
LIVER CELL
PLASMA
MEMBRANE
Cholesterol
Phosphatidylethanolamine
Phosphatidylserine
Phosphatidylcholine
Sphingomyelin
Glycolipids
Others
17
7
4
24
19
7
22
RED BLOOD
CELL PLASMA
MEMBRANE
23
18
7
17
18
3
13
MYELIN
22
15
9
10
8
28
8
MITOCHONDRION
(INNER AND
OUTER MEMBRANES)
3
25
2
39
0
trace
21
ENDOPLASMIC
RETICULUM
6
17
5
40
5
trace
27
Note, molecular weight of cholesterol = 386.7 while that of a typical PC ≈ 760. Thus a
phospholipid : cholesterol ratio of 1 : 1 by mass ≈ 1 : 2 as a molar ratio.
E. COLI
BACTERIUM
0
70
trace
0
0
0
30
Physical properties of lipids & lipid bilayers
Early cell biologists deduced membrane
structure from electron microscopic
images and the knowledge that
membranes were lipoprotein complexes.
They surmised that the electron-opaque
material included phospholipid
headgroups and proteins and that the
electron-transparent membrane material
comprised phospholipid acyl chains.
lipid packing is governed by hydrophobic interactions
At the air-water interface, the hydrophobic tails of a lipid monlayer
avoid association with the water by extending into the air.
Franklin’s Experiment
1 cruet =
1 cubic m =
area =
volume on lake =
area =
thickness = volume/area
2
mL
1000000
mL
0.5
acres
2023
m2
2
mL
2 x 10-6
m3
2023
m2
9.89E-10
m
Franklin investigated the way in which oil could be used to calm water surfaces. He first
performed this experiment on Clapham Pond in the summer of 1771, and subsequently carried
a cane containing a small oil holder to repeat his "conjuring trick" on his travels. He stopped
short of computing the thickness of the mono-layer.
see:
http://www.rsc.org/learn-chemistry/content/filerepository/CMP/00/000/687/
isms-9.pdf?v=1399160447243
lipid packing is also governed by lipid shape
Molecular Molecular
shape
packing
lipid
micelle
water
lipid
bilayer
The cylindrical shape of phospholipids causes them to form extended, disk-like micelles that
are best described as lipid bilayers. Lysolipids and detergents containing only a single acyl
chain form micelles.
Modified from Molecular Biology of the Cell, 4th edition
Energetically unfavorable
phospholipid bilayer
edges exposed to water
sealed phospholipid vesicle
no edges exposed to water
Energetically favorable
Modified from Molecular Biology of the Cell, 4th edition
A. Electron micrograph of a multilamellar phospholipid vesicle in which each layer is a lipid bilayer (After
Bangham, Cambridge Univ)
B. An electron micrograph of a liposome. Its wall, as the diagram indicates, consists of a bilayer (After
Stoekenius, UCSF)
Question
How do we know that the lipid
component of biological
membranes is assembled into
lipid bilayers?
Supporting evidence # 1
The staining pattern of plasma membranes obtained using osmium tetroxide persuaded
scientists that the unstained inner core of the membrane lacked proteins. Hence, it was
assumed that membrane proteins formed beta strands that coated the lipid bilayer. In 1966,
Lenard and Singer, using CD, observed that > 30% of membrane proteins are α-helical. This
made it likely that there were many spherical proteins not just beta strands.
Singer studied phospholipid bilayers and found that they form a flattened surface on water, with
no requirement for a protein coat.
The turning point in the modeling came with the advent of freeze fracture techniques. This
method shows the inside of a membranes and their "bumps, grooves, ridges". These were later
found to be proteins. Supporting Evidence # 2
Paraffin Waxes consist mostly of
straight chain hydrocarbons and are
available in a wide variety of melting
points ranging from 120 to 160 degrees
fahrenheit. Paraffin waxes are mainly
identified in the candle industry by
melting point and oil content.
Wax melting is an endothermic reaction
(heat is absorbed from surroundings).
The 3 types of endothermic phase
changes are the transition from solid to
liquid, the transition from liquid to gas,
and the transition from gas to plasma.
The reverse phase changes are
exothermic (heat is released to the
surroundings).
Monitoring the melting process by Differential Scanning Calorimetry
Inert reference
Actual sample
DSC measures the energy
needed to establish a nearly zero
temperature difference between a
substance and an inert reference
material. Sample and reference
are subjected to identical
temperature regimes and are
heated or cooled at a controlled
rate.
Heat flow
Heat flow
Temp
sensor
Feedback
circuitry to
ensure ∆T = 0
Temp
sensor
The temperatures of the sample and
reference are monitored and
controlled independently using
separate temperature sensors and
heat sources. The temperatures of
the sample and reference are made
identical by varying the power output
from the heat sources.
The energy required to do this is
a measure of the enthalpy or heat
capacity changes in the sample
relative to the reference.
inert sample
material
freezing
a wax
(scan down in T)
endothermic
exothermic
Heat flow
melting a wax
(scan from low to high temp)
Temperature
In fact the baselines of the meting and freezing curves would be superimposable
- they are separated here for illustration purposes only.
Sketch of a lipid bilayer, corresponding electron density profile (−) and definitions of structural parameters. Due
to the soft-matter character of the bilayer stack, features such as headgroup peaks and methyl trough region
are smeared out. In a coarse description using stepwise constant electron densities (−), one can distinguish
water, lipid headgroup, hydrocarbon and methyl trough regions
30
20
Dipalmitoyl-
phosphatidylcholine
bilayers
40
DSC
50˚C
endothermic
1250
Molecular Volume
Å3
1200
note that the increase in molecular
volume ≈ 110 Å3 /molecule ≈ 0.1 m3/
mol ≈ 66 cm3/mol
1150
we will return to this later
1100
P
L
L
X-RAY
67
64
60
carbon chain
packing
20
30
40
Temperature (˚C)
50˚C
endothermic
lipids
Heat flow
(isolated from
membranes & formed
into artificial bilayers)
proteinase K-treated
membranes
(note: these records are displaced in the y-axis to aid comparison)
exothermic
first scan
second scan
10
20
30
40
50
60
Temperature, ˚C
Mycoplasma laidlawii
grown on palmitate
From Melchior et al., (1970) BBA 219, 114-122
Supporting Evidence # 3
Low-angle x-ray diffraction analysis of myelin
membranes
This technique measures the density of matter and can be
used to determine the distribution of lipid and protein in
biomembranes. (a) During development of the nervous
system, a large Schwann cell envelops the axon of a
neuron. The continuous growth of the Schwann cell
membrane into its own cytoplasm, together with rotation of
the nerve axon, results in a laminated spiral of double
plasma membranes around the axon. Mature myelin, a
stack of plasma membranes of the Schwann cell, is
relatively rich in phospholipids. (b) The profile of electron
density — and thus of matter — obtained by x-ray
diffraction studies on fresh nerve, and the relation of this
profile to the protein and lipid components of the myelin
membranes. [Adapted from W. T. Norton, 1981, in G. J.
Siegel et al., eds., Basic Neurochemistry,3d ed., Little,
Brown, p. 68.]
Molecular Cell Biology. 4th edition. Lodish H, Berk A,
Zipursky SL, et al. New York: W. H. Freeman; 2000.
Lipid bilayers are dynamic noncovalent structures
lipids diffuse ≈ 1 µm / sec
1 µm = 1 x 10-4 cm
k ≈ 2 Dm/λ2
t0.5 = 0.693/k
for λ = 3.5 µm
k = 0.164 s-1 and
t0.5 = 4.23 sec
τ = 6 sec
Lipid immiscibility
A series of fluorescence micrographs of vesicles and monolayers of a 1:1
molar mixture of Dipalmitoylphosphatidylcholine (C16) and
dioleoylphosphatidylcholine (C18:1) with varying [cholesterol] in molar %.
The fluorophore (Texas Red Dipalmitoyl Phosphatidyl Ethanolamine) is
concentrated in cholesterol-poor domains
From Veatch & Keller, Phys RevLett 89:268101.
36
detergents - a primer
Surfactants are compounds that lower the surface tension (or interfacial tension) between two liquids or
between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsifiers, foaming agents
and dispersants.
37
physical properties of detergents
Sodium dodecyl sulfate is a detergent with a charged hydrophilic sulfate head group and a 12
carbon hydrocarbon tail. Upon dissolving in water at room temperature (298ºK) it assembles
spontaneously (ΔGº = -16.4 kJ/mol) into a higher ordered micelle with the structure shown below
OO
-O
S
O
S
S
O
O
O
O
O
-O
O
O
-O
S
SDS
-O
O
O
S
O
O
O
O
O
O
S
-O
-O
O-
O
O
O
S
O
O
S
polar
O
S
O
O
O
O
-O
S
O
O
S
O
O
-O
-O
S
O
S
O
O
-O
S
ΔGº = -16.4 kJ/mol = -3.917 kcal/mol
O
at 20ºC, Keq = 10-∆Gº/1.36 = 759
O
O
O
O
O
S
O
S
O
O
-
O-
O
O
O
O
S
O
O-
O-
The critical micelle concentration (CMC) is defined as the concentration of surfactant above
which micelles form and all additional surfactants added to the system form micelles
-O
O
non-
polar
O
O
O
38
HLB is the hydrophilic/lipophilic balance of a molecule and is calculated as: HLB = 20 * MH/M
here MH is the molecular mass of the hydrophilic portion of the molecule, and M is the molecular mass of the
whole molecule, giving a result on a scale of 0 to 20.
39
An HLB value of 0 corresponds to a completely lipophilic/hydrophobic molecule, and a
value of 20 corresponds to a completely hydrophilic molecule.
40
detergent aggregation number
Above the cloud point temp (CMT), nonionic detergents become cloudy and phase separate
into a detergent-rich layer and an aqueous layer. The temperature at which this occurs is called
the cloud point.
41
Questions regarding detergents
• What do you think the effects of a
detergent on a membrane would be?
• What might the advantages of a high
CMC?
• How do you think a large aggregation
number might present a disadvantage?
• How do you think we could use CMT to our
advantage?
Effects of detergents on membranes
•
Detergents solubilize lipid bilayers and integral membrane proteins. This makes detergents v
useful in the purification of membrane proteins.
•
Solubilization involves several intermediate states that have been studied by a variety of
physicochemical and kinetic methods.
•
•
•
•
Solubilization begins by destabilization of the lipid component of the membranes
•
In the final stage of solubilization membrane proteins are present as protomers, with the
membrane inserted sectors covered by detergent. In general binding as a monolayer ring,
rather than as a micelle, is the most probable mechanism.
Detergents insert into the membrane (mass action and hydrophobicity/partitioning).
Detergent insertion transitions from a noncooperative to a cooperative process.
This leads to the formation of membrane fragments of proteins and lipids with detergentshielded edges.
+
+
+
Biochim Biophys Acta. 2000 Nov 23;1508(1-2):86-111.
+
Interaction of membrane proteins and lipids with solubilizing detergents.
le Maire M, Champeil P, Moller JV.
Explaining the basis of the hydrophobic effect -43
The partition coefficient
Nobel, 1974 shows that chemical potential of j (µj)
µj = µjo + R T lnCj + Zj e F ψ
+ V j P + mj g h
µjo = chemical potential of substance j in standard state when
ψ = 0,
h = 0, P and T are standard and Cj = 1M in a particular solvent. As
gravity and ∆P unimportant here,
µj = µjo + R T lnCj + Zj F e ψ
44
Imagine glycerol is added to a mixture of oil and water. The mixture is shaken until the
concentrations of glycerol in oil and water no longer change (equilibrium is achieved).
The mixture is allowed to stand (phase separation occurs) and the oil and water
phases are assayed for glycerol content.
At equilibrium, glyceroloil is in equilibrium with glycerolwater
i.e. µjoil = µjwater
As glycerol is uncharged, an electrical term is not needed and
µ oj oil + RT ln C j oil = µ oj water + RT ln C j water
µ oj oil − µ oj water = RT (lnC j water − lnC j oil)
or K oil/water = exp[( µ oj water − µ oj oil) / RT ]
i.e. K is determined by differences in standard state chemical potential
of j in oil and water
45
Koil/water = exp [(µjowater - µjooil)/RT]
each µjo determined by energetics of interaction
between j and solvent
glycerol has three - OH groups resulting in strong Hbonding to H2O and is thus in a more energetically
favorable state in H2O
∴ µjowater < µjooil
∴ Koil/water < 1.
46
Advantages of a high CMC
•
Dilution of [detergent] to values below the cmc results in the dissociation of micelles to
individual detergent monomers. •
Detergent monomers are much smaller than detergent micelles, and as a result can be
easily removed by dialysis. •
Dialysis is the most common form of detergent removal and this process typically requires
dialyzing the protein detergent mixtures against detergent-free buffer (in about 200-fold
excess) over a period of days. If the protein is a membrane spanning protein, it may be
denatured by detergent removal unless exogenous lipid is added.
•
This technique is more practical with detergents with a high cmc and works best for those
with low molecular weight/small cross-sectional area. •
The technique is unsuitable for detergents with a low cmc, for example, some of the
nonionic detergents.
•
•
Some detergents (e.g. octylglucoside, cholate) are easily removed by dilution ([ ] < CMC).
These techniques permit the biochemist to mix exogenous lipid with detergent-solubilized
integral membrane proteins and then to form sealed proteoliposomes by detergent removal
using either dialysis or dilution/centrifugation.
detergent
removal
+
47
Disadvantages of large aggregation number
•
∆Gº for micelle formation from a long chain detergent is typically strongly negative (micelle
formation is an exergonic reaction). These detergents form large micelles and have v low
CMCs.
•
As a result, such detergents are often “nondialyzable” -they cannot be easily removed by
dialysis or by dilution. •
Such detergents are best removed using hydrophobic resins or beads (e.g. SM2) which
have been developed to have low lipid and protein binding capacities.
•
This technique permits the biochemist to mix exogenous lipid with detergent solubilized
integral membrane proteins and then to form sealed proteoliposomes by detergent removal
using an appropriate resin.
How does SDS denature proteins?
•
Tertiary structure unfolding at submicellar and chain expansion in the micellar range of SDS
concentrations are two major and discrete events in the perturbation of protein structure.
•
The interaction between detergent and protein is predominantly hydrophobic in the
submicellar and exclusively hydrophobic at micellar levels of SDS concentrations.
•
Expansion of the protein chain at micellar concentration of SDS is driven by ionic repulsion
between the protein-bound micelles, micelles and anionic amino acid side chains.
48
Using CMT to our advantage
•
•
•
•
Above the cmt, nonionic detergents become cloudy and phase separate into a
detergent-rich layer and an aqueous layer. The temperature at which this occurs
is called the cloud point. A low cloud point can be advantageous in the solubilization of membrane
proteins, for example, the nonionic detergent Triton X-114 has a cloud point of
22ºC, thus the protein can be solubilized at 0ºC and then brought to 30ºC to
allow phase separation to occur. The membrane protein will then partition into the detergent phase, which can
then be separated by centrifugation.
Can you think of any disadvantages of this methodology?
Lipid Rafts
In fact, these cholesterol rich domains are also
highly enriched in sphingomyelin which is thought
to preferentially associate with cholesterol due to
their complementary geometries.
1
10 mL 5% sucrose
Erythrocyte ghosts were mixed with ice-cold
2
2.5 ml of 1%(v/v) Triton X-100 in TBS and
extracted on ice for 30 min. Extracts were
3
15 mL 35% sucrose
mixed with 2.5 ml of 80% sucrose and
4
overlaid with 15 ml of 35% sucrose and 10
5
ml of 5% sucrose in TBS and
5 mL 40% sucrose
6
ultracentrifuged at 50,000g for 15 hr at 4ºC
Solubilized RBC membranes
allowing the various components in the
mixture to distribute according to their
buoyant density. The top 5 ml was collected
as the first fraction. Proceeding down the
gradient, fractions 2–6 were collected as 5
mL aliquots. Am. J. Hematol. 83:371–375, 2008
Rafts are thought to be involved in signal transduction although some scientists believe they are an
artifact of isolation
For a discussion on lipid rafts see: http://www.bms.ed.ac.uk/research/others/smaciver/Cyto-Topics/lipid_rafts_and_the_cytoskeleton.htm
http://en.wikipedia.org/wiki/Lipid_raft
Phospholipid distribution between hemileaflets of the lipid bilayer
Lipid localization in biological membranes has been carried out
primarily via chemical or enzymatic modification, via exchange
techniques, and in some cases by immunochemical procedures.
The digestion of phospholipids in the outer monolayer of a
membrane by exogenous phospholipases may reveal the
distribution of phospholipids between the two membrane layers. e.g.
•
•
•
•
Phospholipase A2 - releases fatty acids from the second carbon
group of glycerol
Phospholipase C - cleaves phospholipids just before the
phosphate group Phospholipases D - produces phosphatidic acid from
phosphatidylcholine.
Sphingomyelinase breaks SM into phosphocholine and ceramide.
Lipid binding proteins (e.g. BSA) or lipid exchange vehicles (small
unilamellar vesicles) can show which lipids, chemically modified
lipids or enzymatically cleaved lipids are in the external hemileaflet.
Phospholipid distribution between hemi-leaflets of the lipid bilayer
external hemileaflet
Total
% of total phospholipid
50
Sphingomyelin
Phosphatidylethanolamine
0
Phosphatidylcholine
-50
Phosphatidylserine
cytoplasmic hemileaflet
•
What effects could complicate this analysis?
- observer effect.
52
Daleke, D. L. Regulation of transbilayer plasma membrane phospholipid asymmetry. J Lipid Res 2003;44:233-242.
Today’s view of the cell membrane..... (“rafts” not included)
The fluid mosaic model for membrane structure. The fatty acid chains in the interior of
the membrane form a fluid, hydrophobic region. Integral membrane proteins float in this
sea of lipid, held by hydrophobic interactions with their nonpolar amino acid side chains.
Both proteins and lipids are free to move laterally in the plane of the bilayer, but
movement of either from one face of the bilayer to the other is restricted. The
carbohydrate moieties attached to some proteins and lipids of the plasma membrane
are invariably exposed on the extracellular face of the membrane.
Summary - Membranes
1.
Lipids are amphipathic molecules with structurally
diverse hydrophilic and hydrophobic domains
2.
Lipid packing is determined by hydrophobic forces, lipid
shape and lipid physical state
3.
Phospholipids spontaneously assemble as bilayers in
vitro and in vivo
4.
Detergents are surfactants that solubilize membrane
lipids and proteins.
5.
Biomembranes display asymmetric lipid distributions
between bilayer hemi-leaflets and may show lateral
segregation of lipids within each hemi-leaflet
6.
Bilayer-embedded lipids and proteins display high rates
of lateral diffusion but low rates of flip flop