12 - Biological Membranes

Question 1

Biological Membranes

Answer 1

• Separate the cell contents from its surroundings (or divide cell into compartments, i.e. organelles)
• Maintain different (bio)chemical environments between the inside and outside of the cell (or organelles)
• Selectively permeable: “The ability of the cell to discriminate in its chemical exchanges with the environment is fundamental to life…”

Question 2

1915

Answer 2

• Red blood cell (erythrocyte) membranes were first isolated and analyzed
• Found to contain lipids and proteins

Question 3

1925

Answer 3

– E. Gorter and F. Grendel

•Membranes described as a bilayer of phospholipids

Question 4

1935

Answer 4

– H. Davson and J. Danielli
• ‘sandwich model’ – phospholipid bilayer between 2 layers of globular proteins
Two problems:
1. Membranes differ in composition & structure
2. Membrane proteins not very water soluble

Question 5

1972

Answer 5

– S.J. Singer and G. Nicolson

• ‘Fluid Mosaic model’ – proteins inserted into the membrane sheltering the hydrophobic regions from water

Question 6

Evidence for Fluid Mosaic Model

Answer 6

• Freeze-fracture of the membrane

* Membrane proteins “bumps” in the two layers

Question 7

movement of phospholipids

Answer 7

• Phospholipids move laterally very fast, but flip-flopping is quite rare
• A phospholipid can move 2 µm (the length of a bacterial cell) in 1 sec

Question 8

Cholesterol and fluidity

Answer 8

• Cholesterol helps stabilize the membrane:
– High temps (e.g. 37º) reduce movement = less fluid
– Lower temps hinder packing = maintain fluidity

Question 9

Movement of proteins

Answer 9

• Membrane proteins also move laterally

* Frye and Edidin (1970) – fusion studies in mouse and human cells labelled with different markers

Question 10

‘Hop diffusion’ of proteins

Answer 10

2001 - Akihiro Kusumi – ‘hop diffusion’ modification to the Fluid Mosaic Model
• Proteins are ‘fenced-in’ by the cell’s actin cytoskeleton but may ‘hop’ into another area
• Proteins diffuse 100x slower in natural membranes compared to artificial membranes

Question 11

The mosaic nature of membranes

Answer 11

Membranes contain a complex mixture (a ‘mosaic’) of proteins that can be classified into 3 main groups
• Integral proteins (transmembrane protein)
• Peripheral proteins (loosely bound via other proteins)
• Lipid-anchored proteins (covalently attached to lipids, e.g. GPI-anchored)

Question 12

Membrane proteins

Answer 12

Protein structure (hydrophilic and hydrophobic domains) determines how a protein associates with a membrane

Question 13

Membrane carbohydrates

Answer 13

• Short, branched oligosaccharide chains of <15 sugar units
• Highly diverse (between species, individuals, cells)
• Act as identity ‘tags’, e.g. blood groups are due to variation in carbohydrates on the surface of red blood cells
• Most are covalently bound to proteins (glycoproteins)
• Some covalently bound to lipids (glycolipids)

Question 14

Membrane asymmetry

Answer 14

Membranes have distinct inside / outside faces that differ in:
• Lipid composition
• Peripheral proteins attached
• Carbohydrates attached
• Integral proteins are asymmetrical with a defined orientation

Question 15

Membrane Function

Answer 15

Major roles of membranes:
• Compartmentalisation
˗ Cells, organelles (mitochondrion, nucleus, chloroplast, etc.)
˗ Spatial organisation of biochemical reactions
• To provide a selectively permeable barrier
• Cell-to-cell recognition/communication

Question 16

Selectively permeable barrier

Answer 16

• The rate a molecule diffuses across a lipid bilayer depends on:
− Its size
− But mostly on its relative solubility in oil
• Small / hydrophobic molecules cross the membrane easily
• The movement of ions and polar molecules, including H2O, is impeded by the hydrophobic interior of the bilayer
• Highly permeable to small non-polar molecules
• Permeable to uncharged polar molecules depending on size (small > large)
• Highly impermeable to charged molecules (ions)
• Synthetic bilayers 109 times more permeable to water than to Na+ or K+

Question 17

How are ions and large molecules like glucose and amino acids able to move efficiently across biological membranes?

Answer 17

A. Proteins with a hydrophilic channel allowing ions or molecules to diffuse passively from one side to the other
B. Proteins that bind and transport molecules in an energy requiring process
• Transport proteins are usually quite specific for the substance transported

Question 18

Cell-cell recognition

Answer 18

• Some glycoproteins (proteins covalently bound to carbohydrates) act as identification tags that are recognised by receptor proteins in other cells
• The ability to distinguish one type of cell from another is crucial to, e.g.:
− During embryogenesis for the sorting of cells into tissues and organs
− As the basis for recognition and rejection of foreign cells by the immune system

Question 19

Functions of membrane proteins

Answer 19

• Enzymatic activity − Sometimes organised in ‘teams’ to carry out sequential steps in a metabolic pathway
• Signal transduction − Receptors for chemical messengers (signal molecules)
• Intercellular joining − ‘gap junctions’ or ‘tight junctions’
• Attachment to the cytoskeleton and extracellular matrix (ECM)
− coordination of extracellular processes with intracellular processes
− maintains cell shape
− stabilises location of the protein