L03

BIOMEMBRANES:
Composition and
Structural Organization

The presenter invokes the principle of fair use for the use of
copyrighted materials in this presentation.
Learning Outcomes

• discuss the crucial role of biomembranes in the cell;

• illustrate and explain the Fluid-Mosaic Model;
• describe the lipid bilayer, its composition, structural organization,
and properties;
• identify the membrane proteins and cite their role in membrane
functions.
Concept 1: Biomembranes are crucial to the life of the cell.
(Left) Specialized proteins in the cell membrane regulate the concentration of specific molecules inside the
cell © 2010 Nature Education; (Right) This bacterial protein uses light energy to pump protons across
the plasma membrane. (Adapted from H. Luecke et al., Science 286:255–260, 1999)
InFocus: CCR5 and the HIV-resistant man
InFocus: CCR5 and the HIV-resistant man
InFocus: CCR5 and the HIV-resistant man
InFocus: CCR5 and the HIV-resistant man
InFocus: CCR5 and the HIV-resistant man
InFocus: CCR5 and the HIV-resistant man
Concept 2: Cell membranes are dynamic, fluid structures made of lipid
and protein molecules.
 FLUID-MOSAIC MODEL --- Singer and Nicholson (1972)

• All biological membranes are a very thin film of lipid and protein molecules, held together
mainly by noncovalent interactions.
• Cell membranes are dynamic, fluid structures.
– The lipid bilayer provides the basic fluid structure of the membrane and serves as a
relatively impermeable barrier to most water-soluble molecules.
– Most membrane proteins span the lipid bilayer and mediate nearly all of the other
functions of the membrane.
Concept 3: The lipid bilayer provides the basic structure for all cell
membranes.
Concept 3a. Phosphoglycerides, sphingolipids, and sterols are the major
lipids in cell membranes
• amphiphilic = amphipathic
– hydrophilic vs hydrophobic
– self-assembly (spontaneous
bilayer formation in aqueous
environment)
– self-sealing property

• phospholipids
– most abundant membrane lipid
– polar phosphate-based head
• phosphoglyceride (glycerol)
• sphingomyelin (sphingosine)
• READ ON: plasmalogen
– nonpolar hydrocarbon tail
• saturated vs unsaturated
• kinks (cis double bond)
Major phospholipids in mammalian plasma membranes.
Omega-3 fatty acids (highly unsaturated fatty acids found at high concentration
in fish oil) showed beneficial effects.

Incorporated primarily into PE and PC molecules of certain membranes, most

notably in the brain and retina
3a. Phosphoglycerides, sphingolipids, and sterols are the major lipids in
cell membranes

• sphingolipids
– built from sphingosine, a long acyl chain with an amino group (NH2)
and two hydroxyl groups (OH) at one end
– glycolipids have a sugar head group
• READ ON: gangliosides
3a. Phosphoglycerides, sphingolipids, and sterols are the major lipids in
cell membranes

• sterol
– rigid ring structure
– single polar OH group
– short nonpolar
hydrocarbon tail
– intercalate between
phospholipid molecules
to be incorporated into
biomembranes
3b. The lipid bilayer is a two-dimensional fluid structure

• membrane fluidity
– movement of lipid molecules
– rotation
– lateral diffusion
– flip-flop (very rare, why?)

• implication on the formation of lipid bilayer?

– phospholipid translocators
• Fluidity is influenced by:
– Composition
– Temperature

• Phase transition
– shorter chain length
– more unsaturated
– in conformers?

• Cholesterol has an unusual

role in membranes.
– fills gaps between
phospholipids to reduce
the permeability to low-
molecular-weight
solutes
– disrupts the
interactions between
fatty acids, enhancing
membrane fluidity
• Cellular membranes are heterogeneous in composition.

• Lipid rafts are regions of the plasma membrane that accumulate cholesterol and
glycolipids, and has enriched concentration of some transmembrane proteins.
• Because of their composition, raft domains have an increased membrane
thickness and act as microcompartments within the cell, providing an additional
way to spatially organize pathways.
3c. The asymmetry of the lipid bilayer is functionally important

• The lipid compositions of the two monolayers of the lipid bilayer in many
membranes are strikingly different.
• Case in point: human red blood cell
– PC and SM in the outer monolayer
– PE and PS in the inner monolayer
• Lipid asymmetry is important in converting extracellular signals into
intracellular ones.
• Protein kinase C binds to PS-rich region of the cytosolic monolayer as it
requires negatively charged PS for activity
• Phosphatidylinositol is modified by PI 3-kinase to serve as a protein-
binding site
• Upon activation by extracellular signals, phospholipases in the plasma
membrane cleave specific phospholipid molecules, generating fragments
of these molecules (i.e., DAG and IP3) that act as short-lived intracellular
mediators.
• Animals distinguish live and
dead cells by phospholipid
asymmetry of the plasma
membrane.
– In apoptosis, PS, which is
normally confined to the
cytosolic monolayer of the
plasma membrane lipid
bilayer, rapidly translocates
to the extracellular
monolayer.

– translocase inactivated
– scramblase activated
• membrane asymmetry is involved in protective functions, cell-cell
recognition and cell-cell adhesion
Concept 4: Membrane proteins give the cell membrane its characteristic
functional properties.
4a. Proteins interact with the lipid bilayer in different ways.

• integral membrane (transmembrane) proteins

– function on both sides of the bilayer, e.g., transport proteins
• lipid-linked membrane proteins
– exclusively associated with one side of the bilayer only; e.g., signaling proteins
• peripheral membrane (membrane-associated) proteins
– attach to membranes transiently; e.g., Rab GTPases
• Lipid anchors control the membrane localization of some signaling proteins
• Src family of cytosolic protein tyrosine kinases
Membrane proteins are involved in several functions.
4b. Many membrane proteins are glycosylated.

• sugar component added in the lumen of ER and the

Golgi body (glycoproteins) → noncytosolic layer

• disulfide bonds only in the noncytosolic layer

– help stabilize either the folded structure of the
polypeptide chain or its association with other
polypeptide chains
• cell coat or glycocalyx
4c. Membrane proteins can be solubilized and purified in detergent.

• detergents disrupt
hydrophobic associations
and destroy the lipid
bilayer
– small amphiphilic
molecules
– sodium dodecyl
sulfate (SDS) ---
anionic
– Triton X-100 ---
nonionic

• hydrophilic vs
hydrophobic ends

• micelle formation upon

reaching CMC
4d. Many membrane proteins diffuse within the membrane.
BREAK!