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Gaticales CMB Reviewer

Chapter 8: Cellular Membranes


Membrane Functions
1. Compartmentalization

continuous unbroken sheets, enclose


compartments

enclose entire cell


allow specialized activities to occur without
external interference

regulate cellular activities


2. Scaffold for Biochemical Activities

compartment themselves
reactants present, relative position not
stabilized; interaction dependent on random
collisions

membrane provide cell with extensive


framework or scaffolding -> use for effective
interaction
3. Selectively permeable barrier

restrict exchange of molecules from one


side to other

means of communication bet. compartments


they separate

like moat around castle with gated bridges


promote movement of select elements in/out
of cell
4. Transport Solutes

receptors combine with ligands (specific


molecules) or other stimuli (light, mechanical
tension)

diff cells with diff receptors -> capable of


recognizing/ respond to diff. environmental
stimuli

interaction of membrane and ext. stimuli ->


generate signal stimulates or inhibits internal
activity
6. Intercellular interaction

mediate interaction between a cell and


neighbor

recognize to adhere and to exchange


materials and information

proteins may facilitate interaction bet.


extracellular and intracellular cytoskeleton
7. Energy Transduction

energy transduction
photosynthesis
light absorbed by membraned bound
pigments-> chemical energy stored in
carbohydrates

transfer of chemical energy to ATP


in mitochondria/chloroplasts

machinery for physical transporting


substances

from region of low concentration of solute to


region of higher concentration

accumulate substances (sugars, amino


acids, macromolecules)

transport specific ions -> ionic gradients


5. Respond to External stimuli

signal transduction

Brief History of Plasma Membranes

- Ernst Overton (1890)


non polar solutes readily dissolve in
nonpolar solvents

test permeability -> more lipid-soluble solute,


more rapid entrance the root hair cells

- E. Gorter and F. Grendel (1925) proposed that


cell membrane contain lipid bilayer

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extract lipid from RBC measure ant of
surface area of lipid

myelin sheath- low concentration of protein,


more lipid for electrical insulation

plasma membrane only lipid containing


structure

contained bimolecular layer of lipid -> lipid


bilayer

- amphipathic both hydrophilic and hydrophobic

- polar head group face cytoplasm

- 3 types

- hyrdrophobic fatty acyl chains are


protected from contact with H2O

- decrease in surface tension -> presence of


PROTEINS

Hugh Davson & James Danielli (1935)->


plasma membrane lipid bilayer + lined by
globular proteins; (1950) revised: has outer
and inner protein layers and protein
penetrate the membrane (provide polar
solutes and ions entrance to cell)

- Jonathan Singer & Garth Nicolson(1972) Fluidmosaic model

central dogma
focused on physical state of lipid
presented in fluid state; lipid molecules move
laterally within plane of membrane

mosaic of discontinuous particles penetrate


lipid sheet

dynamic structures-> mobile and can engage


in various types of transient or
semipermanent interactions
Chemical Composition of Membranes

- held together by non-covalent bonds


- lipid bilayer (structural backbone, prevent
random movement of water-soluble materials)

- protein (specific functions)


- ratio of lipid-protein depends on type of cellular
membrane, organism, cell; in other words,
depends on the function of membrane in
certain organelle

mitochondrial membrane - high protein/lipid


ratio for protein carriers of ETC

MEMBRANE LIPIDS

1. Phosphoglycerides

phospholipids (contain phosphate grp)


built with glycerol backbone
(phosphoglycerides)

diglycerides (2 hydroxyl grps of glycerol


esterified to fatty acid; 3rd is esterfied to
hydrophilic P group) -> phosphatidic
acid

additional

group: choline
(phosphatidylcholine, PC), ethanolamine
(PE), serine (PS), inositol (PI)

small and hydrophilic + negative


charge P = highly water-soluble at one
end (head group)

@ Physiological pH PS and PI (-); PC and


PE (neutral)

fatty acyl chains are hydrophobic,


unbranched hydrocarbons (16-22
carbons)

membrane FA may be fully saturated (no


double bonds); monounsaturated (one
double bond); polyunsaturated (>1
double)

contain 1 unsaturated and 1 saturated


fatty acyl chain

EPA and DHA (2 highly unsat. FA) contain


5and 6 double bonds in PE and PC (brain
or retina); omega-3 FA
2. Sphingolipids

less abundant membrane lipid


sphingosine - amino alcohol with long
HC chain

sphingosine + FA by its amino group ceramide

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sphingomyelin (phosphoryl choline)
glycolipid- substitiution is a carbohydrate
simple sugar -> cerebroside
includes silica acid ->ganglioside

PE -> inner leaflet for curvature (for budding/


fusion)

PS -> inner binding (+) lysine/arginine


PI -> inner phosphorylated on inositol ring > phosphoinositides (role in transfer of
stimuli)

amphiphatic
FA chains are longer and highly saturated
glycolipids- Nervous system, myelin sheath
(galactocerebroside)
3. Cholesterol

50% of lipid molecules


plant cells contain cholesterol like sterols
small hydrophilic hydroxyl grip toward
membrane surface

hydrophobic rings are flat and rigid ->

MEMBRANE CARBOHYDRATES

- 2-10% by weight (90%) covalently linked to


proteins -> glycoproteins; (10%) linked to
lipids -> glycolipids

- glycosylation - addition of carbohydrates most


complex modifications

- glycoprotein carbohydrate - short branched


hydrophilic oligosaccharides (15 sugars/
chain)

interfere with FA tails of phospholipids

- carbohydrate projection -> mediate interaction

NATURE IMPORTANCE OF LIPID BILAYER

of cell with environment; sorting of membrane


proteins to diff cellular compartments

- important effects on biological properties of

glycolipids of RBC determine A, B, AB, O

membrane

composition determine physical state of


membrane; influence activity of mem.
proteins

provide precursors for highly active chemical


messengers regulate cellular function

flexibility -> membranes are deformable,

Structure and Function of Membrane


Proteins

- grouped into 3 distinct classes:


1. Intergral proteins

shape changee (locomotion, cell div)

facilitate regulated fusion or budding


maintain proper internal composition,
separate charges

self assemble (liposomes)


ASYMMETRY OF MEMBRANE LIPIDS

- lipid bilayer has 2 distinct leafletswith different


lipid composition

transmembrane protein; penetrate lipid


bilayer

2. Peripheral Proteins

entirely outside; either cytoplasmic or


extracellular by noncovalent bonds
3. Lipid-anchored proteins

outside lipid bilayer but are covalently


linked to lipid molecule within bilayer

lipid digesting enzyme cannot fully penetrate


bilayer contains 2 more/less stable
independent monolayers with diff physical
and chemical properties

glycolipids -> outer leaflet serve as receptors


3

INTERGRAL MEMBRANE PROTEINS

- receptors, channels or transporters, agents that


transfer electrons (photosynthesis/ respiration)

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- amphipathic

- crooks in chain where there are double


bonds

- amino acid residues in transmembrane

greater degree of unsaturation: lower

domains form van der Waals with fatty acyl


chains -> seal protein and anchor within bilayer

- DISTRIBUTION OF INTEGRAL PROTEINS:

temperature before bilayer gels

- fatty acid chain length

Freeze- Fracture Analysis

freeze-fracture replication
- structure and properties

shorter: lower melting temperature


- by cholesterol
disrupts close packing of fatty

difficult to isolate in soluble form

abolish sharp transition temperatures;

use of detergent (SDS -> denature protein;

regulate intermediate fluidity

Triton X-100 -> tertiary structure)

increase durability while decreasing


permeability of membrane

PERIPHERAL MEMBRANE PROTEINS

IMPORTANCE OF MEMBRANE FLUIDITY

- weak electrostatic bonds

- perfect compromise between rigid, ordered


structure (mobility is absent) and completely
fluid (mobility present)

- solubilized by extraction with high conc sal


solutions (weaken bond)

- best studied are cytosolic peripheral proteins ->

- allow interaction; assemble proteins at


particular sites to form specialized structures
(junctions, light capturing, synapses)

form fibrillar network as skeleton

- mechanical support; anchor for integral proteins

- membrane growth accomplished by insertion of


lipids and proteins into fluid matrix

- function as enzyme, specialized coats, transmit


transmembrane signals

- allow cell movement, growth, division,


formation of intercellular junctions, secretion,
endocytosis

LIPID-ANCHORED MEMBRANE PROTEINS

- small, complex oligosacch linked to


phosphatidylinositol in outer leaflet

- GPI-anchored proteins- glycosylphosphatidylinositol linkagecontained by


peripheral proteins

- released by phospholipase (cleave inositol


phospholipid)
Membrane Lipids and membrane fluidity

- physical state described by fluidity (viscosity)


- temperature- at which change occur
Saturated FA
- straight flexible rod
- more compact
Cis-unsaturated FA
4

MAINTAIN MEMBRANE FLUIDITY

- lower temperature, response is mediated by


enzymes that remodel membranes make it
cold resistant

desaturating single bonds; form double


bonds (by desaturases - enzymes catalyze
single to double bond)

r e s h u f fl i n g c h a i n s b e t . d i f f e r e n t
phospholipids to form 2 unsaturated FA
(lower temp) (by phospholipases- split FA
from glycerol backbone; acyltransferasestransfer FA)
Lipid Rafts

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- distinctive physical properties, micro domains
tend to float within the more fluid and
disordered environment of artificial bilayer

electrochemical gradient
- solute is an electrolyte (charged)
- charges are opposite, moving process is

Dynamic Nature of Plasma Membrane

- Diffusion of Membrane Proteins after Cell


Fusion

cell fusion- technique 2 different types of


cells fused to produce one cell with common
cytoplasm and single continuous plasma
membrane

fuse by making surface sticky for adhesion;


by addition of inactivated viruses attach to
surface; adding polyethylene glycol, or mild
electric shock

- Restrictions on Protein and Lipid Mobility


fl u o r e s c e n c e r e c o v e r y a f t e r
photobleaching (FRAP)

- if proteins are mobile; random movement


produce gradual appearance of
fluorescence in irradiated circle

single-particle tracking (SPT)


antibody coated gold particles

favorable

- tendency of electrolyte to diffuse depends


on 2 gradients:

chemical gradient - concentration


difference

electric potential gradient- difference in


charge (ex: K+ higher concentration
inside cell)

- Diffusion of Substances through membranes


- Diffusion of Water through membrane
semipermeable
osmosis- lower solute concentration to
higher solute concentration

hypertonic - compartment with high


solute concentration; shrink; plasmolysis

hypotonic- compartment with low solute


concentration; swell;

- Diffusion of Ions through Membranes


highly impermeable to charged substance

- Control of Membrane Mobility


- Membrane Lipid Mobility
lipid diffuse freely before jumping to
neighboring compartment

(Na, K, Ca, Cl)

conductance- rapid movement play role in


formation of nerve impulse, secretion of
substances, muscle contraction, regulation
of cell volume, opening of stomatal pores

Ion channels - permeable to certain ions


Movement of Substances across cell
membranes

- net flux indicate movement of substance influx


and efflux not balanced

- Diffusion
substance move from region of higher
concentration to lower to regulate overall
concentration

depends on random thermal motion of


solutes; exergonic with increase in entropy

1. voltage-gated- difference in ionic


charge on two sides of membrane
2. Ligand-gated channels- binding of
s p e c i fi c
molecule
(ex.
neurotransmitters)
3. M e c h a n o - g a t e d c h a n n e l s mechanical forces(stretch tension)
applied

- KcsA (bacterial K+ ion channel


Facilitated Diffusion
Glucose transporter

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- phosphorylating sugar after entering
cytoplasm, lowering intracellular
glucose conc.

- GLUT1 to GLUT5 (isoforms)


- Insulin secretion increase glucose
transporters

Active Transport
- input of energy
Membrane Potentials and Nerve Impulses

- irritability
- nerve cells (neurons) specialized for collection,
conduction, transmission of information - form
of fast moving electrical impulses

- cell body,dendrites, axon, myelin sheath


- Resting potential
membrane potential
resting potential
action potential - Neurotransmission
synapses- link between neurons
synaptic cleft - narrow gap in synapse
presynaptic cell(receptor) conduct impulse
towards synapse

postsynaptic cell (neuron, muscle, gland cell)


lie on receiving side of synapse

neuromuscular junction- axon and skeletal


muscle ell

synaptic vesicles
neurotransmitters