Chapter 12: Membrane Structure and Function

purpose of membranes

split 2 environments → interior and exterior

what type of interaction laregly make up membranes

many non covalent interactions acting cooperatively

membranes are (symmetric or asymmetric)

asymmetric; 2 faces always differ from each other

charge of cell membrnaes

electrically polarized → internal environment is negative compared to outer environment

what is the thermodynamically favourable structure for most phospholipids and glycolipids in aq

lipid bilayer → result of amphipathic nature, spantaneously forms (hydrophobic effect)

what forces stabilize the bilayer itself

vds forces between hydrocarbon tails, electrostatic + hbonding between polar head groups and water → all thermodynamically favourable interactions

leaflets

opposing monolayers of the lipid bilayer

liposome

ring bilayer that forms when membrane lipid gets sonicated (high freq agitation) in aq environment

liposome applications

study membrane transport, deliver chemicals to cells

lipid bilayer permability to ions and polar molecules

very low permability

3 step process of molecules getting through the bilayer

1. shed off solvation shell (water)

2. dissolve in hydrocarbon core

3. diffuse to other side of membrane; resolvated by water

why are ions impermeable to the lipid bilayer

shedding the solvation shell and replacing it with the nonpolar interactions of the membrane interior is highly unfavourable

how can permability varry depending on sat vs unsat membrane lipids

• sat → denser, stricter

• unsat → kinks, more permiable

are membranes flat

NO! curved; smaller head groups inside

what is Tm

midpoint of the lipid phase transition → big change in fluidity beyond this point

what is Tm (membrane melting point) dependent on

• fatty acid chain length → longer is higher temp

• degree of unsaturation → less is higher temp

how does cholesterol affect membrane fluidity

maintains fluidity, acts like a spacer → OH end H bonds with polar head groups, hydrophobic tail embeds in the membrane core

• lipids cant pack as tight → more fluid

membranes that differ in function will differ in what aspect of structure

protein content → less protein good for insulation, more protein good for current and molecule transport

integral membrane protein

embedded in hydrocarbon chains of membranes, only released when membrane is physically disrupted

peripheral membrane protein

bound to head groups of lipids or exposed part of integral proteins; use electrostatic and hbond interactions (can be intra or extracellular)

what aboout integral membrane protein structure allows it to interact with the hydrophobic fatty acid tails of membrane lipid

often contain membrane spanning α-helice motifs → nonpolar

structure of a porin

• built from β strands, essentially no α-helices

• strands are antiparellel arranged → sheet curls and forms hollow cylinder

  • outside: non polar

  • inside: hydrophillic, water filled

prostaglandin H2 synthase-1 membrane association

associates with part of the ER membrane → set of a-helices w hydrophobic side chains anchor into the membrane on outer surface of ER

lateral diffusion

motion of lipids and membrane proteins within the membrane, rapid and spontaneous

how was lateral diffusion experimentally observed

use fluorescence recovery after photobleaching (FRAP)

• fluorescently label a membrane component

• destroy fluorescent molecules in one area

• if the component is mobile, flurescence in the bleached area will recover; rate depends on its laateral mobility

mobility of proteins within the membrane

vary lots → some as mobile as lipids, some virtually immobile (associate with ECM or cytoskeleton)

fluid mosiac modelq

membranes are two-dimensional solutions of oriented lipids and globular proteins

• bilayer has 2 roles: solvent of integral proteins, permeability barrier between cell compartments

transverse diffussion/flipflopping

transition of a molecule from one membrane surface to the other, slow, controlled (flippases)

• possible for lipids, never been observed yet for proteins

what do transporter proteins determine about the composition of the cell

determine the ionic composition inside a cell → determines its characteristics (since its rxns would be determines by available substrates)

2 factors that determine if a small membrane will cross a membrane

• its [ ] gradients across the membrane

• its solubility in the hydrphobic env of the membrane

lipophillic molecules

dissolve in lipid

simple diffusion

small molecule spantaneously crosses the membrane bcz theres a [ ] gradient and its lipophillic/nonpolar

facilitated diffusion

aka passive transport → polar molecules diffuse down their [ ] gradient using a protein channel/carrier

carrier proteins

transport ions/molecules across the membrane by changing conformation without hydrolysis of ATP

active transport

molecules move against their [ ] gradient, requires energy source

[ ]of k and na in most cells

high [K], low [Na] relative to ecf → generated by Na-K pump

Na-K ATPase pump

active tranport of 3 Na out of the cell and 2 K in → ATP driven pump

p-type ATPase

pump forms a phosphorylated intermediate → phosphoryl group from ATP links to side chain of an aspartate residue in the pump to form phosphorylaspartate

examples of p-type ATPases

Na-K ATPase, Ca ATPase, gastric H-K ATPase, P4-ATPase (flippase)

ATP binding cassettes

the 2 atp binding domains found in multidrug resistance (MDR) proteins → ATP dependent

secondary transport

unfavorable uphill flow (consumes E) of ion/molecule coupled to favorable downhill flow of a different species (provides E)

secondary transporters

aka cotransporters → active transport via secondary transport

• antiporter: molecules move opposite direction

• symporter: molecules move same direction

voltage gated channel

open in response to membrane potential changes

ligand gated channels

open in response to ligands binding (eg neurotransmitters)

uniport

protein that support facilitated diffusion (passive) of one molecule

SGLT

sodium glucose linked transporter; symporter of glucose (against [ ]) and sodium (with [ ]) → faciliated by the gradient Na-K ATPase establishes

selectivity filter

region of ion-channel proteins that determines the specificity of a particular channel

how are potassium channels selective for K structurally

strategic diameter → larger ions too big to enter, small ions can’t interact with the selectivity filter to lose solvated wataer

selectivity filter of potassium channel

2 transmembrane a-helices → 5 aa in the region oriented with their peptide carbonyls pointing into the channel interact with K atoms

• K ions shed their water and instead bind with oxygen of the carbonyls, “pays” for cost of h2o shedding

how does the K+ channel achieve fast transport despite its tight binding for selectivity? 2 models

uses charge repulsion among the4 ion binding sites as the driving force for rapid ion motion. hard knock model nd knock on model

hard knock model of K+ channel

hydrated k enters through unrestricted part of the channel → sheds water and binds to a site in selectivity filter region → each k to bind after “knocks” preceeding k’s further down the channel → k ends up on the other side

critism of the hard knock model

charge repulsion between the ions would be too great for the ions to be in such close contact.

knock on model of K+ channel

K ions never occupy adjacent sites. 4 sites alternately occupy by h2o and K → reduces excessive charge repulsion, but still allows repulsion to be driving force