Alexis Omar López

5 Biological Membranes

Lecture Outline

I. Biological membranes are lipid bilayers with associated proteinsA. Phospholipids form bilayers in water

1. Phospholipids have two fatty acid chains linked to a glycerol molecule

2. The hydrophilic portion of the molecule is the phosphate bonded to the glycerol

3. The fatty acids make up the hydrophobic portion of the molecule4. The molecule is amphipathic

a) The bilayer forms spontaneously because of the amphipathic characteristic

b) Many common detergents are also amphipathic, and so are able to "solubilize" oil

B. Current data support a fluid mosaic model of membrane structure1. Davson and Danielli (1935) – phospholipids form a membrane

two molecules thick: the lipid bilayera) Singer and Nicholson (1972) – the fluid mosaic modelb) This membrane is only 10 nanometers thickc) Various types of proteins move around like icebergs in the

lipid seaC. Biological membranes are two-dimensional fluids

1. Phospholipids act as liquid crystals, and the molecules move laterallya) Fluidity is affected by temperature, among other factors

2. Molecules rarely move from one side of the membrane to the other

3. Frye and Ediden (1970) demonstrated movement of proteins in the membrane

4. Various bonds may occur between hydrocarbon chainsa) Saturated fats lack double bonds in the fatty acid chains,

causing the membrane to be less fluidb) Organisms may alter the proportion of saturation in response

to temperature5. In animal cells, cholesterol, which is slightly amphipathic,

stabilizes the membrane at higher temperatures6. In plant cells, other steroids function in a similar manner

D. Biological membranes fuse and form closed vesicles1. Membrane fusion is due to the liquid crystalline state2. When vesicles and another membrane fuse, their bilayers and

lumens become continuous3. Endocytosis and exocytosis are products of membrane fusion.

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E. Membrane proteins include integral and peripheral proteins1. Integral proteins are firmly bound to the membrane, or are

bound to other lipids that are part of the membrane 2. Transmembrane proteins span the entire bilayer

a) Some transmembrane proteins span the membrane only once, but many weave back and forth a number of times

b) Transmembrane proteins are amphipathicc) The most common type is an alpha helix

3. Peripheral proteins are bound to the hydrophilic ends of the integral proteins

F. Proteins are oriented asymmetrically across the bilayer1. Evidence comes from freeze-fracture electron microscopy2. Proteins are produced in the ER, then pass to the Golgi, then

pass via a vesicle to the plasma membrane3. Various chemical modifications occur along the way

G. Membrane proteins function in transport, information transfer, and as enzymes

1. Membrane proteins are formed by free ribosomes2. Proteins are involved in transport of small molecules3. Enzymes may be embedded in the membrane4. Receptor proteins are embedded in the exterior surface of the

membranea) Signal molecules convert an extracellular signal into an

intracellular signal via signal transduction5. Membrane proteins can serve as identification tags functioning

in cell-to-cell recognition; others form junctions between adjacent cells

II. Cell membranes are selectively permeableA. Most biological membranes are permeable to small or lipid-soluble

molecules1. Water molecules may pass the lipid bilayer2. Gases, small polar molecules, and large hydrophobic substances

may also pass3. Other molecules move through special channels, primarily

through membrane transport membranesB. Random motion of particles leads to diffusion

1. Atoms and molecules above absolute zero exhibit motion2. Due to random motion, particles move from an area of higher

concentration to one of lower concentration, ultimately reaching equilibrium

3. The rate of diffusion depends on temperature, the size of the molecules, electrical charges, and the concentration gradient

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4. Osmosis is the diffusion of water (solvent) across a selectively permeable membranea) The osmotic pressure is the tendency of water to move into

that solutionb) Two solutions may be isotonic to each other, or one may be

relatively hypertonic and the other relatively hypotonic(1) Human cells are isotonic, with a 0.9% sodium chloride

solution(2) Solutions that are hypertonic have a higher osmotic

pressure than the cells; solutions that are hypotonic have a lower osmotic pressure than the cells(a) Animal cells placed in a hypertonic solution tend to

shrivel and die(b) Plant cells, and others with cell walls, placed in a

hypertonic solution tend to plasmolyze(c) Animal cells placed in a hypotonic solution tend to

swell and burst(d) Plant cells placed in a hypotonic solution tend to

become turgid(3) Turgor pressure is the internal hydrostatic pressure

usually present in walled cells(a) Turgor pressure provides structural support in

non-woody plantsC. Carrier-mediated transport of solutes requires special integral

membrane proteins1. Aquiporins are integral membrane proteins that function as

gated water channels2. Impermeability of the cell membrane is advantageous so cells do

not lose valuable polar molecules3. Two forms of carrier-mediated transport are facilitated diffusion

and carrier-mediated active transportD. Facilitated diffusion occurs down a concentration gradient

1. A membrane may become permeable by a protein that combines with the material to be transported

2. Glucose transport across erythrocyte membranes is an example3. Liposomes are artificial vesicles that have been used to study

facilitated diffusionE. Some carrier-mediated active transport systems "pump" substances

against their concentration gradients1. Materials are transported from a region of low concentration to

high by carrier-mediated active transport mechanisms2. ATP is required3. The sodium-potassium pump is an example4. Other mechanisms involve the pumping of ions in photosynthesis

and aerobic respiration, which results in a membrane potential and electrochemical gradient

F. Linked cotransport systems indirectly provide energy for active transport

1. These transport systems cotransport molecules against their concentration gradient

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2. ATP is a requirement for linked cotransport systems3. Example: glucose transport across microvilli of the intestine4. More than one transport system may transport one substance

G. Facilitated diffusion is powered by a concentration gradient; active transport requires another energy source

1. The energy of ATP is used directly or indirectly in transport of materials

H. The patch-clamp technique has revolutionized the study of ion channels

1. This was first developed in the mid 1970s at the Max Planck Institute in Germany

2. With this technique, scientists can study single ion channels of even very small cells over time

I. In exocytosis and endocytosis, large particles are transported by vesicles or vacuoles

1. In exocytosis, the cell expels wastes or a secretory producta) Exocytosis also results in growth of the cell membrane

2. In endocytosis, a cell takes up materialsa) Phagocytosis involves taking in solid materialsb) Pinocytosis involves taking in liquid droplets

3. Receptor-mediated endocytosis involves the bonding of receptor proteins to the material to be engulfeda) Molecules bind to receptors, called ligands, concentrated in

coated pits(1) Coated pits are formed by a protein, clathrin

b) The coated pits move inwards, via endocytosis, and are then termed coated vesicles

c) The coated vesicle ultimately becomes an endosome when the coating is lost

d) Cholesterol is taken into cells by this pathway(1) Brown and Goldstein– 1986 Nobel Prize

III. Cell Signaling is the mechanism by which cells communicate with one anotherA. An example of a molecule that is a cell signal is cyclic adenosine

monophosphate (cAMP)1. This is clearly illustrated when studying slime molds

B. Cell signaling involves 6 steps1. Synthesis and release of the signaling molecules

a) Signaling molecules may be neurotransmitters, hormones, or other types of molecules

b) Signaling molecules are ligands (often called the first messengers), which specifically bind to receptors on the target cells

c) Some ligand-receptor complexes bind to and activate specific integral membrane proteins: the G proteins

2. Transport to target cells3. Reception of the information by target cells

a) This is typically composed of a transmembrane protein with a functional portion on the extracellular surface

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b) Typically there are three domains: an external domain for docking by the signaling molecule, a second domain extending through the plasma membrane, and a third domain resembling a "tail" that extends into the cytoplasm

4. Signal transductiona) In this process, cells convert and amplify an extracellular

signal into an intracellular one5. Response by the cell

a) The tail undergoes a conformational change, which then activates a sequence of proteins that initiate changes within the cytoplasm

b) The G proteins may pass the message to the second messenger, often cyclic AMP

c) The second messengers typically activate protein kinases6. Termination of signaling

IV. Junctions are specialized contacts between cellsA. Anchoring junctions connect epithelial cells

1. A common form of anchoring junction, desmosomes, are points of attachment between some animal cellsa) Desmosomes hold cells subject to mechanical stresses

togetherb) Desmosomes are composed of intermediate filaments, which

span the gap between two cellsB. Adhering junctions cement cells together with proteins

1. Tight junctions seal off intercellular spaces between some animal cells

2. Tight junctions seal cells tightly with protein links3. Tight junctions are important in epithelia

C. Gap junctions permit transfer of small molecules and ions1. Gap junctions contain pores that connect cells2. Proteins form the pores3. Gap junctions allow rapid chemical and electrical communication

between cells4. The apertures of gap junctions may be controlled

D. Plasmodesmata allow movement of certain molecules and ions between plant cells

1. Plasmodesmata are connections between plant cells2. Plasma membranes are continuous through the plasmodesmata3. A desmotubule may connect the ER of adjacent cells4. Typically, molecules, but not organelles, pass through

plasmodesmata

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Research and Discussion Topics

Cystic fibrosis is due to a defect in a membrane pump of the cell membrane. Discuss the causes and treatments of this disease.

Discuss the mechanism by which cells use receptor-mediated endocytosis to take in cholesterol. Investigate the connection to the genetic disorder, familial hyper-cholesterolemia (FH).

Compare and contrast the blood-brain barrier to the blood-testes barrier. How are they similar? How are they different? What are the clinical applications of these two barriers?