Lipid Asymmetry and Transport

 
A remarkable feature of several biological membrane systems is that their phospholipids are asymmetrically distributed across the lipid bilayer, a phenomenon called membrane phospholipid asymmetry. Most of our knowledge on phospholipid asymmetry of lipids has come from studies on human erythrocytes. The aminophospholipids, phosphatidylethanolamine (PE) and in particular phosphatidylserine (PS) are preferentially located in the inner leaflet of the membrane bilayer, while the other major components sphingomyelin (SM) and phosphatidylcholine (PC) are more abundant in the outer leaflet. It is assumed that phospholipids are also distributed asymmetrically in the plasma membrane of most, if not all, nucleated cells. Three distinct mechanisms for transmembrane movement of phospholipids have been described: (i) spontaneous diffusion (ii) facilitated diffusion and (iii) ATP-dependent, active translocation (Fig.1). Active transport
ATP-dependent
(e.g. Aminophospholipid-translocase for PS+PE
in plasma membrane)		 Spontanous diffusion
ATP-independent
Plasma membrane phospholipid asymmetry plays a crucial role in a variety of biological processes . Fig.1 Mechanisms of Lipid transmembrane movement
Most of our current knowledge on the kinetics of phospholipid transmembrane movement in cell membranes has been gained using phospholipid analogues in translocation assays.  
Considerable insight into the kinetics of phospholipids transmembrane movement in cell membranes has been gained from assays using phospholipid analogues. These analogues are tagged in some way (fluorescence, spin-label, radioactivity) so as to be able to track them through the assay procedure. The fatty acid chain-labeled phospholipid analogues contain either a fluorescent group (7-nitrobenz-2-oxa-1,3-diazol-4-yl) or a spin-label (see figure below) on a short fatty acid chain linked to the sn-2 position of the phospholipid's glycerol backbone. Our laboratory has experience in synthesizing spin-labeled phospholipid analogues. ...back
The information gleaned from those translocation assays has been used to formulate mathematical models which allow calculation of the transmembrane movement and distribution of phospholipids.  
 
Results and Conclusions:
 
  Transmembrane movement of phospholipids in the plasma membrane of myoblasts
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  Translocation of phospholipids in the plasma membrane of sperm cells
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  Redistribution of phospholipids in the plasma membrane of fibroblasts
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  Translocation of phospholipids in the plasma membrane of hepatocytes
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  Transmembrane movement of phospholipids in the plasma membrane of yeast cells
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  Relevance of phospholipid asymmetry in endocytosis
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