February 23, 1995

Chapter 12 Biological Membranes

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Overview: what do we want to understand?

A. Structural aspects

fluid mosaic model

lipid bilayer

directionality

dynamic nature of membrane

B. Functional aspects

transport of solutes

transport of biomolecules

signal transduction

A. Structural aspects

fluid mosaic model:

lipid bilayer with polar "head" groups at surface and hydrophobic "tails" internal

directionality: asymmetric distribution of lipids and membrane proteins

dynamic, not static, structure: transverse (leaflet to leaflet or side to side migration; relatively slow process) as well as lateral diffusion (migration on one leaflet or face of a membrane; relatively fast process) are possible

evidence to support this model?

1. impact of structure of fluidity: predictions based on bilayer model are borne out by structural changes in lipid structures:

cis-double bond in "tail" produces a "kink" in the chain, reduces van der Waals interactions, and increases fluidity (shifts gel/liquid transition temperature to lower values)
introduction of rigid steroid, like cholesterol, has similar impact on fluidity
increasing the length of the hydrocarbon "tail" increases van der Waals interactions, and decreases fluidity (shifts gel/liquid transition temperature to higher values)

2. study of synthetic membranes (i.e., liposomes)

3. physical studies of membranes (EM/freeze fracture)

notes on membrane proteins

type characteristics

integral spans both sides or leaflets

transmembrane domain(s): hydrophobic amino acids, a-helix

peripheral weak association: ionic or H-bonding

lipid-anchored protein attached to lipid and lipid provides anchor to

membrane

B. Functional aspects

key points for us to cover: transport of solutes; transport of biomolecules; signal transduction

1. transport of solutes

how are solutes (large and small, charged and uncharged) transported across the membrane?

channels and pores

passive transporters

active transporters

a. channels and pores

pore: a passageway through adjacent phospholipids used by uncharged, non-

polar solutes (terminology "pore" used principally in reference to bacteria)

channel: passageway through bilayer lined by hydrophilic groups and used by

polar solutes; lining is either an integral protein or an ionophore; may or may not be gated (ligand or voltage) (terminology "pore" used principally in reference to

e.g., gramicidin S: an antibiotic ionophore (where ionophore is defined as a lipid soluble structure that facilitates ion-transport across a membrane)

b. passive transport (facilitated diffusion)

solute binds to a protein; a conformational change occurs; and the solute is subsequently released on the other side of the membrane
solute moves down a concentration gradient

e.g., glucose transporter (glucose represented by circles)

e.g., anion exchange protein ("band 3"): chloride and bicarbonate ions bind and are co-transported, thereby maintaining electroneutrality

c. active transport

solute moves "up" a concentration gradient, a process that requires an energy source such as: [1] the hydrolysis of energy rich compound (e.g., ATP); [2] the simultaneous transport of a second solute down a concentration gradient; or [3] molecular modification of solute

example 1: Na⁺,K⁺-ATPase, an electrogenic pump (i.e., one that generates a charge differential across a membrane)

example 2: simultaneous or co-transport as in the glucose transporter

example 3: molecular modification of solute

2. transport of biomolecules

prokaryotes: multicomponent system in outer membranes

eukaryotes: exo and endocytosis using specialized lipid vesicles

3. signal transduction

process: signal (first messenger) to transducer to effector enzyme to second messenger to cytosolic/nuclear effectors to response

three principal signal transduction systems

adenylate cyclase

inositol phospholipids

receptor tyrosine kinases

example: adenylate cyclase cascade triggered by epinephrine