PART 1 STRUCTURE AND MODELS OF BIOLOGICAL MEMBRANES

Membrane Structure and Function Membrane Structure  Lipids and proteins are the main components of the membranes, although carbohydrates are also important.  The most abundant lipids in most membranes are phospholipids  Phospholipids and most of proteins of membrane are amphipathic molecules. Amphipathic molecules : A molecule that has both hydrophilic region and a hydrophobic regions. The membrane ia a fluid mosaic : The membrane is a fluid structure with various protein embedded in or attached to a double layer (bilayer)of phospholipids.

Membrane lipids are organized in a bilayer The proteins are scattered throughout the bilayer (perform most membrane functions)

Structure of the Cell Membrane Outside of cell Inside of cell (cytoplasm ) Lipid Bilayer

Fluid Mosaic Model of the cell membrane

History of the Plasma Membrane 1665: Robert Hooke  1895: Charles Overton - composed of lipids  ’s: must be a phospholipid  1925: E. Gorter and G. Grendel - phospholipid bilayer  1935: J.R. Danielli and H. Davson – proteins also part, proposed the Sandwich Model  1950’s: J.D. Robertson – proposed the Unit Membrane Model  1972: S.J. Singer and G.L. Nicolson – proposed Fluid Mosaic Model

Plasma Membrane Models Overton model (1895)  the layers surrounding cells “lipoids” made from lipids and cholesterol.

Plasma Membrane is made of Phospholipids Gorter + Grendel –Red Blood Cells analyzed –cell membranes are made of two opposing thin lipid double layers –polar head groups pointing toward the aqueous environment (Polar heads face out and Nonpolar tails face in) –fails to account for the manifold of functions attributed to cell membranes. (Does not explain why some nonlipids are permeable)

Plasma Membrane Models Sandwich Model (Danielli + Davson) Earlist model for the biomembrane structure including proteins. The proteins possess hydrophobic interiors and a water-containing outer layer. Proteins are adsorbed to the lipophilic layers surrounding cells The water-containing regions of protein layers adsorped on lipid layers are permeable for charged solutes

Plasma Membrane Models Sandwich Model (Danielli + Davson) 2 layers of globular proteins with phospholipid inside to make a layer and then join 2 layers together to make a channel for molecules to pass

Plasma Membrane Models Sandwich Model (Danielli + Davson) Divalent cations as calcium form complexes with lipids or proteins that reduce their interaction with water. Therefore membranes containing calcium are less permeable for ions. Arguments did not exclude the possibility that the proteins may span the membrane such that a “mosaic” of protein-rich and lipid-rich regions is formed due to the lack of experimental evidence.

Plasma Membrane Models Unit Membrane Model (Robertson) Outer layer of protein with phospholipid bilayer inside, believed all cells same composition, does not explain how some molecules pass through or the use of proteins with nonpolar parts, used transmission electron microscopy

Plasma Membrane Models Fluid Mosaic Model (Singer + Nicolson) Phospholipid bilayer with proteins partially or fully imbedded, electron micrographs of freeze-fractured membrane

Which membrane model is correct? 1) Rapidly freeze specimen 2) Use special knife to cut membrane in half 3) Apply a carbon + platinum coating to the surface 4) Use scanning electron microscope to see the surface According to the electron micrograph which membrane model is correct? Why? Fluid-Mosaic M odel

Mosaic – means an object comprised of bits and pieces embedded in a supporting structure. (1) membrane lipids form the supporting structure.  (2) membrane proteins provide the bits and pieces.  (3) both lipids and proteins may be mobile or 'fluid'

Fluid-Mosaic Model Fluid – the plasma membrane is the consistency of olive oil at body temperature, due to unsaturated phospholipids. (cells differ in the amount of unsaturated to saturated fatty acid tails)  Most of the lipids and some proteins drift laterally on either side. Phospholipids do not switch from one layer to the next. (Both proteins and lipid bilayer move in plane)

Structure of the Plasma Membrane

Membranes are mosaics of structure and function A membrane is a mosaic of different proteins embedded and dispersed in the phospholipid bilayer. These proteins vary in both structure and function, and they occur in two spatial arrangements 1- Integral Proteins 2- Peripheral proteins

1- In tegral proteins, which are inserted into the membrane:  penetrate the hydrophobic core of the lipid bilayer, often completely spanning the membrane (a transmembrane protein).  Their hydrophilic ends are exposed on both sides of the membrane.  cannot easily be separated from the lipids.  form the major fraction of membrane proteins.

2- Peripheral proteins, which are not embedded in the lipid bilayer but attached to the membrane surface:  May be attached to integral proteins or held by fibers of the extracellular matrix.  On the cytoplasmic side, may be held by filaments of cytoskeleton  are only loosely attached to the membrane surface  can easily be separated from the membrane by mild treatment

Carbohydrate Polymers form:  Glycolipids when attach to Phospholipid Molecules  Glycoproteins when they attach to proteins  act as Cell Receptor Sites  involved in Cell Signalling in the Immune System.

Cholesterol effect on Membrane Fluidity  At Warm Temp.  making the membrane Less fluid by restraining the phospholipid movement  At Cold Temp.  making the bilayer more fluid at lower (cool) temperatures by preventing close packing of phospholipids.

Structure of the Plasma Membrane Phospholipid bilayer  Phospholipid –Hydrophilic head –Hydrophobic tails  Cholesterol  Proteins –Transmembrane/ Intrinsic/Integral –Peripheral/Extrinsic  Cytoskeletal filaments  Carbohydrate chain  Glycoproteins  Glycolipids

Proteins of the Plasma Membrane Provide 6 Membrane Functions: 1) Transport Proteins 2) Receptor Proteins 3) Enzymatic Proteins 4) Cell Recognition Proteins 5) Attachment Proteins 6) Intercellular Junction Proteins

1) Transport Proteins Channel Proteins – channel for lipid insoluble molecules and ions to pass freely through Carrier Proteins – bind to a substance and carry it across membrane, change shape in process

2) Receptor Proteins – Bind to chemical messengers (Ex. hormones) which sends a message into the cell causing cellular reaction

3) Enzymatic Proteins – Carry out enzymatic reactions right at the membrane when a substrate binds to the active site

4) Cell Recognition Proteins – Glycoproteins (and glycolipids) on extracellular surface serve as ID tags (which species, type of cell, individual). Carbohydrates are short branched chains of less than 15 sugars

5) Attachment Proteins Attach to cytoskeleton (to maintain cell shape and stabilize proteins) and/or the extracellular matrix (integrins connect to both). -Extracellular Matrix – protein fibers and carbohydrates secreted by cells and fills the spaces between cells and supports cells in a tissue. -Extracellular matrix can influence activity inside the cell and coordinate the behavior of all the cells in a tissue.

6) Intercellular Junction Proteins – Bind cells together –Tight junctions –Gap junctions