Biochemical aspects

Learning objectives At the end of lecture student should be able to Describe the structure of cell membrane Explain molecular basis of cell membrane Name different types of membrane protein Correlate functions with structure of membrane

Membranes (highly fluid & Dynamic structure) Plasma membranes form closed compartments around cellular protoplasm to define cell boundaries. It shows selective permeability – acts as a barrier, maintaining differences in composition between the inside and outside of the cell. – Done by specific proteins named transporters and ion channels. The plasma membrane exchanges material with the extracellular environment by – Exocytosis – endocytosis, and – gap junctions

Membranes (highly fluid & Dynamic structure) plays key roles in cell–cell interactions and in transmembrane signaling. Membranes also form specialized compartments within the cell. (organelles), eg, – mitochondria, – ER, – sarcoplasmic reticulum, – Golgi complexes, – secretory granules, – lysosomes, and – nuclear membrane. Membranes localize enzymes, function as integral elements

Membranes (highly fluid & Dynamic structure) Changes in membrane structure affect water balance and ion flux and therefore every process within the cell. Specific deficiencies or alterations of certain membrane – Familial Hypercholesterolemia – Cystic Fibrosis – Wilson’s disease – Hereditary Spheriocytosis – Metastasis of Cancer cells In short, normal cellular function depends on normal membranes.

Membrane structure is visible using an electron microscope. Transmission electron microscopes (TEM) can show the 2 layers of a membrane. Freeze-fracturing techniques separate the layers and reveal membrane proteins.

Membrane structure Cellular membranes have 4 components: 1. Phospholipid bilayer 2. Transmembrane proteins 3. Interior protein network 4. Cell surface markers

MEMBRANE STRUCTURE The fluid mosaic model of membrane structure contends that membranes consist of: phospholipids arranged in a bilayer globular proteins inserted in the lipid bilayer

Phospholipid structure consists of glycerol – a 3-carbon polyalcohol acting as a backbone for the phospholipids 2 fatty acids attached to the glycerol phosphate group attached to the glycerol

PHOSPHOLIPIDS The fatty acids are nonpolar chains of carbon and hydrogen. – Their nonpolar nature makes them hydrophobic (“water-fearing”). – The phosphate group is polar and hydrophilic (“water-loving”).

PHOSPHOLIPIDS The partially hydrophilic, partially hydrophobic phospholipid spontaneously forms a bilayer: -fatty acids are on the inside -phosphate groups are on both surfaces of the bilayer

Phospholipids Phospholipids bilayers are fluid. -hydrogen bonding of water holds the 2 layers together -individual phospholipids and unanchored proteins can move through the membrane -saturated fatty acids make the membrane less fluid than unsaturated fatty acids -warm temperatures make the membrane more fluid than cold temperatures

MEMBRANE PROTEIN Membrane proteins have various functions: 1. Transporters 2. Enzymes 3. Cell surface receptors 4. Cell surface identity markers 5. Cell-to-cell adhesion proteins 6. Attachments to the cytoskeleton

(1) a single a helix, (2) as multiple a helices, or (3) as a rolled-up b sheet (a barrel). Some of these "single-pass" and "multipass" proteins have a covalently attached fatty acid chain inserted in the cytosolic lipid monolayer. Other membrane proteins are exposed at only one side of the membrane. (4) Some of these are anchored to the cytosolic surface by an amphipathic a helix that partitions into the cytosolic monolayer of the lipid bilayer through the hydrophobic face of the helix. (5) Others are attached to the bilayer solely by a covalently attached lipid chain either a fatty acid chain or a prenyl group in the cytosolic monolayer or, (6) via an oligosaccharide linker, to phosphatidylinositol in the non cytosolic monolayer. (7, 8) Finally, many proteins are attached to the membrane only by non-covalent interactions with other membrane proteins.

MEMBRANE PROTEIN Peripheral membrane proteins -Anchored to a phospholipids in one layer of the membrane -Possess nonpolar regions that are inserted in the lipid bilayer -Are free to move throughout one layer of the bilayer

MEMBRANE PROTEIN Integral membrane proteins -span the lipid bilayer (transmembrane proteins) -nonpolar regions of the protein are embedded in the interior of the bilayer -polar regions of the protein protrude from both sides of the bilayer

MEMBRANE PROTEIN Integral proteins possess at least one transmembrane domain -Region of the protein containing hydrophobic amino acids -Spans the lipid bilayer

MEMBRANE PROTEINS Extensive nonpolar regions within a transmembrane protein can create a pore through the membrane. -  sheets in the protein secondary structure form a cylinder called a  -barrel -  -barrel interior is polar and allows water and small polar molecules to pass through the membrane

Cells are sugar coated Sugar moieties of glycolipid protruding outward in plasma membrane. No sugar on inside

Permeability coefficient of membrane Water, urea, glycerol, indole, tryptophan, glucose, O 2,CO 2 & N can easily pass Na, K Cl lag behind

Lipid raft, caveolae, & tight junctions

PASSIVE TRANSPORT

ACTIVE TRANSPORT