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MEMBRANE STRUCTURE AND FUNCTION

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STRUCTURE

1. Membrane models.2. Fluid mosaic of lipids, proteins, and

carbohydrates.3. Selective permeability.4. Passive transport. Osmosis.5. Active transport.6. Exocytosis and endocytosis

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The cell membraneThe plasma membrane is the boundary that separates the

living cell from its nonliving surroundings.

Membranes are of crucial importance to life, because a cell must separate itself from the outside environment for two major reasons.

1. It must keep its molecules of life ( DNA , RNA , and its

assortment of proteins ) from dissipating away.

2. It must keep out foreign molecules that damage or destroy the cells components and molecules.

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1. Membrane models1895, Charles Overton – membranes are made of lipids;

1917, Irving Langmuir – artificial membrane;

1925, E. Gorter and F. Grendel – phospholipid bilayer two molecules sick;

1935, H. Davson and J. Danielli – sandwich model: a phospholipid layer between two layers of globular protein;

1950, electron microscopy of cells confirmed the “sandwich model”;

1972, S. Singer and G. Nicolson – fluid mosaic model.

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Two generations of membrane models(a) The Davson-Danielli model, proposed in 1935,

sandwiched the phospholipid bilayer between two protein layers.

With later modifications, this model was widely accepted until about 1970.

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Two generations of membrane models(b) The fluid mosaic model disperses the proteins and

immerses them in the phospholipid bilayer, which is in a fluid state.

Shown here in simplified form, this is our present working model of the membrane.

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Singer and Nicolson proposedProteins are individually embedded in the phospholipid bilayer, rather than forming a solid coat spread upon the surface.

Hydrophilic portions of both proteins and phopholipids are maximally exposed to water resulting in a stable membrane structure

Hydrophobic portions of proteins and phospholipids are in the nonaqueous environment inside the bilayer.

Membrane is a mosaic of proteins inserted in a fluid bilayer of phospholipids.

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The cell membrane

The cell membrane functions as a semi-permeable barrier, allowing a very few molecules across it while fencing the majority of organically produced chemicals inside the cell.

The most common molecule in the model is the phospholipid, which has a polar (hydrophilic) head and two nonpolar (hydrophobic) tails.

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Diagram of a phospholipid bilayer

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Artificial membranes (cross sections)

(a) Water can be coated with a single layer of phospholipid molecules.

The hydrophilic heads of the phospholipids are immersed in water, and the hydrophobic tails are excluded from water.

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Artificial membranes(b) A bilayer of phospholipids forms a stable boundary between two aqueous compartments.

This arrangement exposes the hydrophilic parts of the molecules to water

and shields the hydrophobic parts from water.

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Cell membrane EM

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2. The fluid mosaic of lipids, proteins and carbohydrates

A membrane is held together primarily by hydrophobic interactions, which are much weaker than covalent bonds.

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Movement of phospholipids Most of the lipids and some of the proteins can drift in the plane of the membrane but not from one layer to another.

Lateral movement(frequent)

Flip-flop(rare)

Phospholipids move quickly along the membrane’s plane averaging 2 microM per second. Proteins drift more slowly.

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Evidence for the drifting of membrane proteins When researchers fuse a human cell with a mouse cell, it takes less than an hour for the membrane proteins of the two species to completely mix in the membrane of the hybrid cell.

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Membrane fluidity

Tails with kinks are keeping molecules from packing together, enhancing membrane fluidity.

Fluid

Saturated hydrocarbon tails

Viscous

Unsaturated hydrocarbon tails with kinks

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Cholesterol within the membrane Cholesterol reduces membrane fluidity by reducing phospholipid movement at moderate temperatures and also hinders solidification at low temperature: it makes the membrane less fluid at warm t and more fluid at lower t.

Cholesterol

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Cell membrane

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Sidedness of the plasma membraneThe membrane has distinct

cytoplasmic and extracellular sides.

This bifacial quality is determined when the membrane is first synthesized and modified by the ER and Golgi.

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Sidedness of the plasma membraneThe diagram color-codes the

two sides of the membranes of the endomembrane system,

to illustrate that the side facing the inside of the ER, Golgi, and vesicles

is topologically equivalent to the extracellular surface of the plasma membrane.

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Sidedness of the plasma membraneThe other side always faces

the cytosol,

from the time the membrane is made by the ER

to the time it is added to the plasma membrane by fusion of a vesicle.

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Sidedness of the plasma membraneThe small green "trees"

represent membrane carbohydrates that are synthesized in the ER and modified in the Golgi.

Vesicle fusion with the plasma membrane is also responsible for secretion of cell products (purple).

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Cell recognition by membrane carbohydratesCell-cell recognition – the ability of a cell to determine if

other cells it encounters are alike or different from itself.

Cell-cell recognition is crucial in the functioning of an organism. It is the basis for:

•Sorting of an animal embryo’s cells into tissues and organs

•Rejection of foreign cells by the immune system

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Cell recognition by membrane carbohydrates

Because of their diversity and location, likely candidates are membrane carbohydrates:

•Branched oligosaccharides

•Some covalently bonded to lipids (glycolipids)

•Most covalently bonded to proteins (glycoproteins)

•Vary from species to species, between individuals of the same species and among cells in the same individual

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Mosaics of Structure and FunctionThe plasma membrane and the organelles membranes each have unique collections of proteins.

Integral proteins are transmembrane proteins with hydrophobic regions that completely span the hydrophobic interior of the membrane.

The hydrophobic regions consist of one or more stretches of nonpolar amino acids.

The hydrophilic ends are exposed to aqueous solutions on either side of the membrane.

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Mosaics of Structure and Function

Peripheral proteins are not embedded in the lipid bilayer; they are either bound to the surface of the membrane or to the integral protein.

To give an animal cell a stronger external framework, frequently membrane proteins are attached either to cytoskeleton from cytoplasmic side or to the fibers of the extracellular matrix from the exterior side.

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The structure of a transmembrane proteinThis ribbon model highlights the alpha-helical secondary structure of the hydrophobic parts of the protein,

which lie mostly within the hydrophobic core of the membrane.

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The structure of a transmembrane proteinThis particular

protein, bacteriorhodopsin, has seven transmembrane helices (outlined with cylinders for emphasis).

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The structure of a transmembrane proteinJoining the helices are

hydrophilic polypeptide segments that together form the parts of the protein in contact with the aqueous solutions on either side of the membrane.

Bacteriorhodopsin is a specialized transport protein found in certain bacteria.

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Transport

ATP(a) (b)

(a) A protein that spans the membrane may provide a selective hydrophilic channel across the membrane.

(b) Some transport proteins hydrolyze ATP as an energy source to actively pump substances across the membrane.

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Enzymatic activity Membrane protein may be an enzyme. Often several enzymes are ordered as a team that carries out sequential steps of a metabolic pathway.

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Signal transduction A membrane protein may have a binding site with a specific shape that fits the shape of a chemical messenger, such as hormone.

The external messenger (signal) may cause a conformational change in the protein that relays the message to the inside of the cell.

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Intercellular joining

Membrane proteins of adjacent cells may be hooked together in various kinds of junctions

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Cell-cell recognition

Some glycoproteins (proteins with short chains of sugars) serve as identification tags that are specifically recognised by other cells

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Attachment to cytoskeleton and extracellular matrix (ECM)

Mycrofilaments may be bonded to membrane proteins, a function that helps maintain cell shape and fixes the location of certain membrane proteins.

Proteins that adhere to the ECM can coordinate extracellular and intracellular changes.

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The diffusion of solutes across membranes(a) A substance will diffuse from

where it is more concentrated to where it is less concentrated.

The membrane, viewed here in cross section, has pores large enough for molecules of dye to pass.

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The diffusion of solutes across membranesDiffusion down the concentration gradient leads to a dynamic equilibrium; the solute molecules continue to cross the membrane, but at equal rates in both directions.

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The diffusion of solutes across membranes(b) In this case, solutions of two different dyes are separated by a membrane that is permeable to both dyes.

Each dye diffuses down its own concentration gradient.

There will be a net diffusion of the green dye toward the left, even though the total solute concentration was initially greater on the left side.

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Selective permeability: traffic across membranesSugars, amino acids, and other nutrients enter the cell;

metabolic waste products leave the cell.

The cell takes in oxygen for cellular respiration and expels carbon dioxide.

It regulates its concentrations of inorganic ions (Na+, K+, Ca2+, Cl-) by shuttling them across the membrane.

To be able to accomplish all this functions the cell membrane have to be selectively permeable – not to allow substances to cross the barrier indiscriminately.

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Selective permeability: traffic across membranes

Hydrophilic molecules such as ions and polar molecules have problems to travel across the hydrophobic core of the membrane themselves.

In contrast, hydrophobic molecules: hydrocarbons, CO2, and O2, can dissolve in the membrane and cross it with ease.

The key role in the regulation of the transport across the membrane belongs to transport proteins.

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Selective permeability: traffic across membranesHydropobic molecules avoid the transport proteins, whereas hydrophilic have to interact with them.

Transport proteins either build hydrophilic channel which allows travelling through the hydrophobic part

or serve as carrier by binding to passengers and physically moving them across.

In both cases the protein is very specific for the substances it moves.

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Passive transport is diffusion across a membraneThe tendency to spread out into available space - diffusion is the result of thermal motion (intrinsic kinetic energy). It is a movement of a substance down a concentration gradient.

Diffusion continues until the dynamic equilibrium concentration is reached.

In order to reach equilibrium any substance will diffuse down its concentration gradient – regular, graded concentration change over a distance in a particular direction

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Passive transport is diffusion across a membrane

Since any system has a tendency to entropy, diffusion of a solute in water is a spontaneous process which requires no energy.

Oxygen is constantly diffusing into the cell during cellular respiration.

A substance diffuses down its own concentration gradient and is not affected by the gradients of other substances.

The diffusion of a substance across a biological membrane is called passive transport (the cell requires no energy).

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Passive transport is diffusion across a membrane

Spontaneous process which is a function of a concentration gradient when a substance is more concentrated on one side of the membrane.

Passive process which does not require the cell to expend energy. It is the potential energy stored in a concentration gradient that drives diffusion.

Rate of diffusion is regulated by the permeability of the membrane, so some molecules diffuse more freely than others.Water diffuses freely (although not easily) across most cell membranes.

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Cells and Diffusion

Water, carbon dioxide, and oxygen are among the few simple molecules that can cross the cell membrane by diffusion (or a type of diffusion known as osmosis).

Diffusion is one principle method of movement of substances within cells, as well as the method for essential small molecules to cross the cell membrane.

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Cells and Diffusion

Carbon dioxide is produced by all cells as a result of cellular metabolic processes.

Since the source is inside the cell, the concentration gradient is constantly being replenished/re-elevated, thus the net flow of CO2 is out of the cell.

Metabolic processes in animals and plants usually require oxygen, which is in greater concentration outside the cell, thus the net flow of oxygen is into the cell.

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OsmosisOsmosis is the passive transport of water across a semi-permeable membrane.

Hypertonic solution – a solution with a greater solute concentration than that inside a cell.

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OsmosisHypotonic solutions – a solution with a lower solute concentration compared to that inside a cell

Isotonic solutions have equal (iso-) concentrations of substances (as compared to that inside a cell).

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Osmosis

Water potentials are thus equal, although there will still be equal amounts of water movement in and out of the cell, the net flow is zero.

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The water balance of living cellsWater diffuses down its concentration gradient:If two solutions of different concentrations are separated by a selectively permeable membrane that is permeable to water but not to solute, water will diffuse from the hypoosmotic solution to the hyperosmotic.

Direction of osmosis is determined by the difference in total solute concentration, regardless of the type or diversity of solutes in the solutions.

Osmotic concentration – total solute concentration of a solution

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The water balance of living cells How living cells react to changes in the solute concentrations of their environments depends on whether or not they have cell walls. Animal cells do not have cell walls; plant cells do.

Unless it has special adaptations to offset the osmotic uptake or loss of water, an animal cell fares best in an isotonic environment.

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The water balance of living cellsPlant cells are generally healthiest in a hypotonic environment, where the tendency for continued uptake of water is balanced by the elastic wall pushing back on the cell.

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One model for facilitated diffusionThe transport protein (purple) alternates between two conformations, moving a solute across the membrane as the shape of the protein changes.

The protein can transport the solute in either direction, with the net movement being down the concentration gradient of the solute.

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Passive Transport Passive transport requires no energy from the cell. Examples include the diffusion of oxygen and carbon dioxide, osmosis of water, and facilitated diffusion.

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Active TransportActive transport requires the cell to spend energy, usually in the form of ATP. Examples include transport of large molecules (non-lipid soluble) and the sodium-potassium pump.

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Voltage across membranes

Because anions and cations are unequally distributed across the plasma membrane, all cells have voltages across their plasma membranes.

Membrane potential - voltage across membranesRanges from -50 to -200mv. As indicated by the negative sign, the cell’s inside is negatively charged with respect to the outside.

Affects traffic of charged substances across the membrane

Favors diffusion of cations into cell and anions out of the cell (because of electrostatic attractions)

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The sodium-potassium pump:This transport system pumps ions against steep concentration gradients.

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The sodium-potassium pump:The pump oscillates between two conformational states in a pumping cycle that translocates three Na+ ions out of the cell for every two K+ ions pumped into the cell.

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The sodium-potassium pump:ATP powers the changes in conformation by phosphorylating the transport protein (that is, by transferring a phosphate group to the protein).

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An electrogenic pumpProton pumps are examples of membrane proteins that store energy by generating voltage (charge separation) across membranes. Using ATP for power, a proton pump translocates positive charge in the form of hydrogen ions.

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An electrogenic pumpThe voltage and H+ gradient represent a dual energy source that can be tapped by the cell to drive other processes, such as the uptake of sugar and other nutrients. Proton pumps are the main electrogenic pumps of plants, fungi, and bacteria.

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CotransportAn ATP-driven pump stores energy by concentrating a substance (H+, in this case) on one side of the membrane. As the substance leaks back across the membrane through specific transport proteins, it escorts other substances into the cell.

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CotransportIn this case, the proton pump of the membrane is indirectly driving sucrose accumulation by a plant cell, with the help of a protein that cotransports the two solutes.

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Carrier-assisted Transport The transport proteins are highly selective.

Some of these proteins can move materials across the membrane only when assisted by the concentration gradient, a type of carrier-assisted transport known as facilitated diffusion (glucose).

The rapid breakdown of glucose in the cell (a process known as glycolysis) maintains the concentration gradient.

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Carrier-assisted Transport In the case of active transport, the proteins are having to move against the concentration gradient.

For example the sodium-potassium pump in nerve cells.

Na+ is maintained at low concentrations inside the cell and K+ is at higher concentrations.

The reverse is the case on the outside of the cell.

When a nerve message is propagated, the ions pass across the membrane, thus sending the message.

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Carrier-assisted Transport After the message has passed, the ions must be actively transported back to their "starting positions" across the membrane.

This is analogous to setting up 100 dominoes and then tipping over the first one.

To reset them you must pick each one up, again at an energy cost.

Up to one-third of the ATP used by a resting animal is used to reset the Na-K pump.

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Types of transport molecules Uniport transports one solute at a time. Symport transports the solute and a cotransported solute at the same time in the same direction.

Antiport transports the solute in (or out) and the co-transported solute the opposite direction. One goes in the other goes out or vice-versa.

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EndocytosisEndocytosis - the incorporation of materials from outside the cell by the formation of vesicles in the plasma membrane.

Phagocytosis is the type of endocytosis where an entire cell is engulfed.

Pinocytosis is when the external fluid is engulfed.

Receptor-mediated endocytosis occurs when the material to be transported binds to certain specific molecules in the membrane.

Examples include the transport of insulin and cholesterol into animal cells.

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Endocytosis

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Reading

Ch. 7 (125-141)