12 - Biological Membranes Flashcards
Biological Membranes
- 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…”
1915
- Red blood cell (erythrocyte) membranes were first isolated and analyzed
- Found to contain lipids and proteins
1925
– E. Gorter and F. Grendel
•Membranes described as a bilayer of phospholipids
1935
– 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
1972
– S.J. Singer and G. Nicolson
• ‘Fluid Mosaic model’ – proteins inserted into the membrane sheltering the hydrophobic regions from water
Evidence for Fluid Mosaic Model
- Freeze-fracture of the membrane
* Membrane proteins “bumps” in the two layers
movement of phospholipids
- 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
Cholesterol and fluidity
• Cholesterol helps stabilize the membrane:
– High temps (e.g. 37º) reduce movement = less fluid
– Lower temps hinder packing = maintain fluidity
Movement of proteins
- Membrane proteins also move laterally
* Frye and Edidin (1970) – fusion studies in mouse and human cells labelled with different markers
‘Hop diffusion’ of proteins
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
The mosaic nature of membranes
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)
Membrane proteins
Protein structure (hydrophilic and hydrophobic domains) determines how a protein associates with a membrane
Membrane carbohydrates
- 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)
Membrane asymmetry
Membranes have distinct inside / outside faces that differ in:
• Lipid composition
• Peripheral proteins attached
• Carbohydrates attached
• Integral proteins are asymmetrical with a defined orientation
Membrane Function
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
Selectively permeable barrier
• 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+
How are ions and large molecules like glucose and amino acids able to move efficiently across biological membranes?
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
Cell-cell recognition
• 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
Functions of membrane proteins
• 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
