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I. Introduction

A. Cell (plasma) membrane: defines cell boundaries
B. Internal membranes define a variety of cell organelles

1. Nucleus
2. Mitochondria
3. Endoplasmic reticulum (rough and smooth)
4. Golgi apparatus
5. Lysosomes
6. Peroxisomes
7. Chloroplasts
8. Other

II. Membrane Functions

A. Form selectively permeable barriers
B. Transport phenomena

1. Passive diffusion
2. Mediated transport

a. facilitated diffusion

(1) carrier proteins
(2) channel proteins

(a) non-gated channels
(b) gated channels

b. active transport

C. Cell communication and signaling
D. Cell-cell adhesion and cellular attachment
E. Cell identity and antigenicity
F. Conductivity

III. Fluid Mosaic Model of Membrane Structure

A. Mosaic: an object comprised of bits and pieces embedded in a supporting structure

1. membrane lipids form the supporting structure
2. membrane proteins provide the bits and pieces
3. both lipids and proteins may be mobile or 'fluid'

B. Membrane lipids: the supporting structure

1. phospholipids
2. glycolipids
3. cholesterol

C. Membrane proteins: the bits and pieces

1. integral (intrinsic) proteins
2. peripheral (extrinsic) proteins

IV. The Membrane Lipids

A. phospholipids

1. most abundant of the lipids in membranes: form a lipid bilayer
2. phospholipid composition

a. glycerol backbone covalently linked to:
b. two long, non-polar fatty acid hydrocarbon chains
c. variable phosphate-containing polar group

3. phospholipids are amphiphilic (amphipathic) molecules:

a. hydrophobic ('water fearing') end: fatty acid chains

orient toward the interior of the membrane

b. hydrophilic ('water 'loving') end: phosphate group end

orients towards the extracellular space or cytoplasm

4. some common membrane phospholipids

a. choline containing phospholipids

(1) phosphatidycholine
(2) sphingomyelin

b. non-choline containing phospholipids

(1) phosphatidylserine
(2) phosphatidylethanolamine
(3) phosphatidylinositol

5. synthesis occurs in the membranes of the endoplasmic reticulum

All of the phospholipids are initially synthesized on the cytoplasmic side of the lipid bilayer. The phospholipids containing choline tend to get flipped to the opposite face of the lipid bilayer (which is topologically equivalent to the extracellular space) by enzymes known as 'flippases'. Once 'flipped', further flip-flopping is rare.

B. Glycolipids

1. least common of the membrane lipids (~2%)
2. always found in outer leaflet of plasma membrane*

*Or the topological equivalent of the outer leaflet of the plasma membrane, i.e., the luminal facing leaflet of an organelle membrane. Thus there are almost no membrane bound carbohydrates that protrude into the cytoplasm of a cell.

3. general structure of a glycolipid is a variation on the phospholipid theme

a. two long hydrocarbon chains

(1) hydrophobic, non-polar part of molecule

b. carbohydrate component: one or more sugars

(2) hydrophilic, polar part of molecule

4. synthesis of glycolipids

a. starts in membranes of endoplasmic reticulum
b. carbohydrates added in Golgi apparatus

C. Cholesterol

1. steroid; lipid soluble; found in both leaflets of lipid bilayer
2. amphiphilic: -OH group forms the polar end of the molecule
3. synthesized in membranes of endoplasmic reticulum

Summary of Membrane Lipids


V. Membrane Proteins

A. Integral (intrinsic) proteins

1. penetrate the bilayer or span the membrane entirely
2. can only be removed from membranes by disrupting the phospholipid bilayer
3. types:

a. transmembrane proteins

(1) single-pass
(2) multiple-pass

Trans-membrane proteins have membrane spanning portions containing alpha helically arranged sequences of 20-25 hydrophobic amino acids. Short strings of hydrophilic amino acids separate the hydrophobic sequences from each other: These hydrophilic stretches tend to be found exposed to the more aqueous environments associated with the cytoplasm or the extracellular space.

b. covalently tethered integral membrane proteins

Tethered integral membrane proteins may be largely exposed to either the cytoplasm or aqueous extracellular space, but are covalently linked to membrane phospholipids or glycolipids

4. many integral proteins are glycoproteins

a. covalently linked via asparagine, serine, or threonine to sugars

The sugars of glycoproteins are exclusively found on the extracellular side of the membrane or topological equivalent

5. synthesis of integral proteins:

a. occurs in the rough endoplasmic reticulum
b. many integral proteins wind up as glycoproteins

(1) glycosylation begins in lumen of er
(2) carbohydrates are modified in Golgi

6. integral proteins often form protein complexes having multiple subunits

7. functions

a. enzymatic
b. receptors
c. transport
d. communication
e. adhesion

B. Peripheral (extrinsic) proteins

1. do not penetrate the phospholipid bilayer
2. are not covalently linked to other membrane components
3. form ionic links to membrane structures

a. can be dissociated from membranes
b. dissociation does not disrupt membrane integrity

4. located on both extracellular and intracellular sides of the membrane

a. often link membrane to non-membrane structures

5. synthesis of peripheral proteins:

a. cytoplasmic (inner) side: made in cytoplasm
b. extracellular (outer) side: made in er and exocytosed

VI. Membrane Dynamics

A. Lipid Asymmetry

1. phospholipids are asymmetrically distributed within the lipid bilayer

a. outer leaflet of plasma membrane

(1) phosphatidylcholine
(2) sphingomyelin

b. inner leaflet of plasma membrane

(1) phosphatidylethanolamine
(2) phosphatidylserine*

*carries a net negative charge

c. flippase helps establish the phospholipid asymmetry

2. glycolipids exclusively found on outer half of membrane

B. Lipid Mobility

1. mobility of membrane lipids:

a. rotational movement
b. lateral movement

The lipids (especially the phospholipids) are mobile within their half of the lipid bilayer. Flip flop to the opposite side of the membrane is rare. Mobility of the phospholipids tends to increase as the number of double bonds ('kinks') between adjacent carbon atoms in the fatty acid chains increase.

2. cholesterol effects on membrane fluidity:

At high temperatures cholesterol tends to reduce membrane fluidity, probably by interacting with the hydrocarbon tails of the phospholipid and glycolipid molecules. At low temperatures cholesterol helps prevent membranes from freezing and thus tends to maintain membrane fluidity.

C. Protein Asymmetry

1. many different kinds of proteins are in the cell membranes

a. each type has a unique conformation and orientation
b. flip flop of proteins does not occur
c. conformational changes of protein can occur

2. carbohydrates of glycoproteins always at outer surface

a. help form the 'glycocalyx' (along with glycolipids)

D. Protein Mobility

1. rotational mobility
2. lateral diffusion

Protein mobility can vary greatly. Some proteins are free to move. Others may be tethered to structures in the cytoplasm or extracellular spaces, thus restricting their movement. Some types of cell junctions (e.g., tight junctions) can restrict protein movements to a specific membrane domain.

E. Membrane Protein Conformational Changes

1. help explain many many membrane functions
2. concept:

The binding of a membrane protein/glycoprotein to some other cellular or extracellular substance, molecule, ion, etc. can/will result in a 3-dimensional conformational change in that membrane protein.

That conformational change can/will, in turn, drive or inhibit some other cellular event.

Example 1: facilitated diffusion

Example 2: signaling




 Page Published by: Steve Downing
Department of Anatomy and Cell Biology
School of Medicine
University of Minnesota-Duluth
The University of Minnesota is an equal opportunity educator and employer.
© 1997 by the Regents of the University of Minnesota
Page Coordinator: Steve Downing (sdowning@d.umn.edu)
Last Modified: April 23, 1997