Membranes

(Lecture 7):

Membranes are very fluid in order to allow proteins inserted into the membrane
(integral membrane proteins or transmembrane proteins) to interact with each
other.

Usually membrane proteins are integrated into the membrane by means of one or
multiple alpha-helices. This works if all amino acids making up the alpha-helix are
hydrophobic, because their side chains are pointing outward interacting with the
lipids, whereas the hydrogen bonds needed to stabilize the alpha-helix are all along
the length of the alpha-helix cylinder. The insertion of membrane proteins into the
lipid bilayer introduces an asymmetry, because integral membrane proteins can
only move laterally, not vertically. This means the side of the protein pointing
outward never changes, the protein just moves around within the plane of the
membrane (like phospholipids).

Freeze fracture splits membranes into two lipid leaflets; why? Because freezing
tightly binds phospholipids to surrounding water molecules by hydrogen bonds,
whereas the two lipid leaflets are held together only by van der Waals forces (in the
frozen state).

The main function of membranes is to serve as a barrier and to selectively transport
molecules the cell needs or wants to get rid of. To analyze membranes, scientists
prepare a beaker of water separated into two compartments. The divider contains a
small hole covered with an artificial membrane. Then solutes can be added on one
side, and after a certain time one can measure the solute concentration on the other
side. This experiment tells you that membranes are selectively permeable. Gases
like oxygen, and small polar molecules like water pass freely across the membrane.
Large charged molecules can barely cross the membrane, and ions not at all.

Whenever there is a different concentration of substances across the membrane,
this gives rise to the phenomenon of diffusion: the passive mixing of substances
resulting in net transport along the concentration gradient.
To fill this dry definition with some life, imagine a bouqet of roses in the middle of a
room; you all know that as you step closer, they will smell more strongly: there is a
concentration gradient of scent molecules mixing with air molecules. If you throw
out the roses, what happens with the concentration gradient? It will get flatter and
flatter. You can see that if you draw a window a certain position away from the
origin x=0, where the molecules all start out from, more and more molecules move
into that window over time (net movement away from the source).

The movement of individual molecules is, of course, random, and is owing to
Brownian motion, the random walk of individual molecules because of thermal
motions and collisions.

You have Brownian motion in a water glass, but no diffusion; add a drop of ink, still
Brownian motion, but now also diffusion, because the ink will equally
distribute/diffuse throughout the glass of water. In other words, diffusion occurs as
long as there is a concentration gradient (-G). When a small molecule like glycerol
is equally distributed on both sides of the membrane, it still moves back and forth
across the membrane, but there is no more net movement, hence no more diffusion
(G=0).

High temperature, small molecule size, short distance also speed up diffusion.

As water is such an important molecule in biology, the diffusion of water across a
selectively permeable membrane is called osmosis.

If you place 1.05L of water next to 200g of NaCl dissolved in 1L of water (1.05L of
solution), there are much fewer water molecules in the solution (0.05L less water),
therefore water will move into the solution (along its concentration gradient).

Hypertonic solution: ocean water cannot quench your thirst, because water will flow
out of your cells to dilute the ocean water.

Hypotonic solution: tap water, net water flow into cells. Tap water is the least toxic
substance, but you can still kill yourself by drinking water: Untrained marathon
runner drinking several liters of water.

Isotonic: same solute concentration as inside the cell, therefore no net water flow.

To transport molecules like ions or large polar molecules across the membrane,
cells need integral membrane proteins. They come in two flavors: those that just
facilitate diffusion (passive transport), and those that transport molecules against
their concentration gradient (active transport).
Passive transport: facilitated diffusion
1. gated channel proteins: ions flow along their electrochemical gradient when
the channel is open
2. carrier protein
Glucose carrier: binding of sugar to either side causes a conformation change in the
carrier protein resulting in transport of sugar to the other side. Sugar can be
transported in both directions! In contrast to channel proteins, carrier proteins can
be saturated because they must bind their substrate, i.e. at one point the rate of
diffusion cannot increase further because all carrier proteins are occupied.
Saturation does not happen with channel proteins. Channel proteins are always
gated, that is, they are closed in their default state, and open upon changes in
electricity or binding of regulators. Channel proteins transport ions along their
concentration gradient.

Importantly, both channels and carriers can transport substances only along the
concentration gradient (thats why its called facilitated diffusion)!

Active transport moves substances against their concentration gradient, and
therefore requires energy.

This is subdivided into primary active transport, which directly relies on ATP
hydrolysis to overcome the +G of transporting something against its concentration
gradient, and secondary active transport, which uses the energy from the
concentration gradient set up by primary active transport.

Most important example: Sodium potassium pump in animals to counteract
hypotonic drinking water, not found in plants, because they have a stable cell wall
that prevents bursting of cells upon water inflow. The sodium potassium pump
moves three sodium ions out and two potassium ions in (a net movement of one ion
out). This controls osmolarity, generates the resting potential, and sets up ion
gradients.

Secondary active transport systems use gradients established by the sodium
potassium pump. An important example is the sugar sodium cotransporter, which
uses the energy from sodium inflow to transport sugar into cells with a high interior
concentration of sugar. The best example is the cells lining the gut, whose task is to
take up nutrients from the food we eat. To maximize the uptake of sugar, these cells
use a sodium sugar cotransporter to take up every sugar molecule from the gut
lumen (where the digesting food passes by). On the other side the sugar crosses the
membrane into the extracellular fluid with a sugar carrier, because these sugar
molecules are constantly removed/shipped to the rest of our body.