Ch12 Membrane Structure and Function

What makes a good membrane?

• selective barrier - lets some things through, blocks others; identifies self from non-self

• flexible structure - can bend without breaking

• self-assembling - forms spontaneously in water

• asymmetric - inside down not = outside

• dynamic - components can move around

fluid mosaic model

many different types of molecules all come together to make the whole

Amphipathic lipids

this is why they form spontaneously

hydrophilic head

hydrophobic tail

Why do membranes form spontaneously?

• water molecules are highly ordered around hydrophobic substances

• entropy increases when hydrophobic tails cluster together

• no covalent bonds needed - it’s all about thermodynamics

result: lipid bilayer formation is energetically favorable

Membrane permeability rules: what can cross easily?

small, nonpolar molecules (O2, CO2)

small, uncharged polar molecules (H2O)

Membrane permeability rules: what is blocked?

ions (Na+, K+, Cl-) high energy cost to remove water shell

large polar molecules (glucose, amino acids)

charged molecules

hydrophobicity and size determine permeability of molecules

Rank these molecules from most to least likely to cross a lipid bilayer easily:

• Sodium ion (Na+)

• Ethanol (CH3CH2OH)

• Glucose (C6H12O6)

• Carbon dioxide (CO2)

CO2, CH3CH2OH, C6H12O6, Na+

Membrane fluidity: the goldilocks principle

too fluid = problems

• membrane loses integrity

• proteins can’t function properly

too rigid = problems

• membrane can crack

• transport processes shut down

just right = functional

• flexible enough for protein function

• stable enough for barrier function

decreasing melting temperature means it will be fluid for longer (shift left on curve) making it more permeable; vice versa

Fatty acid composition: saturated fats

more rigid

straight chains packed tightly

higher melting temperature

Fatty acid composition: unsaturated fats

more fluid

kinks from double bonds prevent tight packing

lower melting temperature

• cis unsat will increase fluidity

• trans double bonds will look and act like the fully saturated fatty acids because they do not introduce kinks

Controlling membrane fluidity

chain length: longer = more rigid, shorter = more fluid

cholesterol: acts as a fluidity buffer in animal cells

Choose: Cholesterol will increase/decrease fluidity at lowered temperatures and will increase/decrease fluidity at higher temperatures.

increase; decrease

Scenario: bacteria living in hot springs (80 C) vs arctic bacteria (0 C)

Question: how would their membrane lipid composition differ to maintain proper fluidity

think about what chains would help each environment

• long saturated chain to counter the hot spring

• higher degree of CIS unsaturation of short chains for cold

hot: things are moving around too much so we want to increase the number of hydrophobic interactions via increasing chain length (increase number of atoms)

Cholesterol: fluidity buffer

high temperature: restrains phospholipid movement, decreasing fluidity

low temperatures: prevents membranes from becoming too rigid (crystalline), increasing fluidity

Effect of cholesterol on different membrane composition

saturated membranes: tends to disrupt packing and introduce spacing, increasing fluidity

unsaturated membranes: cholesterol tends to fill gaps created by kinds in unsaturated chains, decreasing fluidity

Cholesterol-like molecules in other species

bacteria: hopanoids

plants: sterols

There are four lipid bilayers composed of varying ratios of saturated fatty acids, unsaturated fatty acids, and cholesterol. Assume all bilayers are at the same, physiological temperature

• Membrane A: high saturated, low unsaturated, no cholesterol

• Membrane B: high unsat, low sat, no chol

• Membrane C: high sat, low unsat, high chol

• Membrane D: high unsat, low sat, high chol

Rank the membranes from most fluid to least fluid under these conditions

B > D > C > A

2 main categories of membrane proteins: integral proteins

embedded in or spanning the membrane

have hydrophobic regions that interact with lipid tails

ex. ion channels, transporters

2 main categories of membrane proteins: peripheral proteins

associated with membrane surface

easily removed from membrane

usually interact with polar head groups

• protein structure determines membrane association

Passive transport

no energy needed - move down gradient (high conc. to low conc.)

• simple diffusion, facilitated diffusion (aquaporins for H2O)

Active transport

energy required; move against gradient

• primary active transport (ATP), secondary activate transport (using energy gradient set up by something else)

proteins make membranes selectively permeable

Scenario: a cell needs glucose when internal glucose is already higher than external glucose

• is the glucose trying to move with or against its gradient?

• what type of transport is needed

• what energy source would be required?

• how might the cell accomplish this?

against

active

ATP

protein transporters

Primary active transport: Na+/K+ pump

pumps 3 Na+ out and 2K+ in per ATP

maintains membrane potential

drive secondary transport processes

uses ~30% of cell’s total energy

essential for nerve function

target of important drugs (digitalis)

• mechanism: P-type ATPase with phosphorylation intermediate

Secondary active transport: Na+/Glucose symporter

uses one gradient to drive transport of another molecule

Na+ gradient powers glucose uptake

primary pumps create gradients that power secondary transport

antiporter - Na+ drives Ca2+ removal

Ion channels

highly selective: specific ion types only

extremely fast: millions of ions per second

regulated: can open and close (gated)

ex. K+ channel

• selectivity filter perfectly fits K+ ions

• change repulsion creates rapid transport

• demonstrates structure function relationship

Clinical insight: what is Tetrodotoxin (TTX)?

potent neurotoxin produced by pufferfish (fugu)

also found in blue ringed octopus, some frogs, and bacteria

lethal dose: 1-2 mg for humans

how does TTX works?

it selectively blocks voltage-gated Na+ channels

binds to channel opening and physically plugs the pore

prevents Na+ influx —> blocks nerve depolarization and signal propagation

results in paralysis and respiratory failure

You discover bacteria in a high-salt environment. Predict three membrane-related adaptations they might have and explain why each would be beneficial.

cell needs to counteract salt in and H2O out

osmotic pressure - high salt will try to get rid of H2O (crenation)

too much salt is coming in

• downregulate aquaporin to prevent H2O out

• cell might adapt to exploit the salt gradient —> 2nd transport, brings in something like glucose or push out what it doesn’t need

• upregulate active transport, push more salt out like Na+/K+