Membrane Assymetry The lipid bilayer can be divided into two faces, the noncytosolic monolayer, the outer

membrane; and cytosolic layer which is the inner membrane. The lipid compositions of these individual layers are different from each other. Thus, there is lipid asymmetry across the lipid bilayer, between the noncytosolic and cytosolic layers. An inside-outside asymmetry is produced. Each layer has a different composition of glycerophospholipids and sphingolipids. The choline-containing phospholipids (phosphatidylcholine and sphingomyelin) are located mainly in the outer membrane; the aminophospholipids (phosphatidylserine and phosphatidylethanolamine) are frequently observed in the inner layer. With this lipid asymmetry, there is limited transverse movement (flip flop1) of the membrane phospholipids, usually extremely slow. The asymmetry accounts for some of the functional difference in the two layers. For example, when a cell undergoes apoptosis, the phosphatidylserine normally localized to the cytoplasmic leaflet is transferred to the outer surface: there it is recognized by a macrophage which then actively scavenges the dying cell. The asymmetry of lipids is maintained by lipid transporters, which catalyzed the movement of specific lipids from one layer to the other with the use of ATP. Specific proteins that bind individual phospholipids also appear to be present in the two leaflets, contributing the asymmetric distribution of these lipid molecules. The class of enzymes flippase catalyzed the transfer of lipids from the one side of the membrane to the other. This class of enzymes includes floppase and scramblase. Floppase is an outward directed ATP-dependent transporter which transfers lipid in the opposite direction. Scramblase facilitates bidirectional mixing of phospholipids between the two leaflets or layers and lipids are transferred in a random manner contributing to the cell membrane s asymmetry. As mentioned before, the characteristics of the noncytosolic monolayer is different from the cytosolic monolayer. First, the fluidity of one side of the membrane is different from the other. Second, there will be a difference in the charged groups on the two faces which contribute to the membrane potential. Third, the glycolipids and glycoproteins in the outer membrane of the plasma membrane contribute to the identification of the cell. Self-sealing capability Endocytosis In endocytosis, the cell engulfs some of its extracellular fluid (ECF) including material dissolved or suspended in it. A portion of the plasma membrane is invaginated and pinched off forming a membranebounded vesicle called an endosome. Phagocytosis ("cell eating"):
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1

results in the ingestion of particulate matter (e.g., bacteria) from the ECF. The endosome is so large that it is called a phagosome or vacuole.
Flip-flop of lipids (from one half of a bilayer to the other) is normally very slow. Flip-flop would require the polar head-group of a lipid to traverse the hydrophobic core of the membrane. The two leaflets of a bilayer membrane tend to differ in their lipid composition

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Phagocytosis occurs only in certain specialized cells (e.g., neutrophils, macrophages, the amoeba), and occurs sporadically.

In due course, phagosomes deliver their contents to lysosomes. The membranes of the two organelles fuse. Once inside the lysosome, the contents of the phagosome, e.g. ingested bacteria, are destroyed by the degradative enzymes of the lysosome. Pinocytosis In pinocytosis ("cell drinking"), the drop engulfed is relatively small. Pinocytosis
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occurs in almost all cells occurs continuously

Clathrin-mediated endocytosis is mediated by small (approx. 100 nm in diameter) vesicles that have a morphologically characteristic crystalline coat made up of a complex of proteins that are mainly associated with the cytosolic protein clathrin. Clathrin-coated vesicles (CCVs) are found in virtually all cells and form domains of the plasma membrane termed clathrin-coated pits. Coated pits can concentrate large extracellular molecules that have different receptors responsible for the receptormediated endocytosis of ligands, e.g. low density lipoprotein, transferrin, growth factors, antibodies and many others. Exocytosis, also known as 'reverse pino-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane. These membrane-bound vesicles contain soluble proteins to be secreted to the extracellular environment, as well as membrane proteins and lipids that are sent to become components of the cell membrane.

Flip-flop of lipids (from one half of a bilayer to the other) is normally very slow. Flip-flop would require the polar head-group of a lipid to traverse the hydrophobic core of the membrane. The two leaflets of a bilayer membrane tend to differ in their lipid composition

Flip-flop of lipids (from one half of a bilayer to the other) is normally very slow. Flip-flop would require the polar head-group of a lipid to traverse the hydrophobic core of the membrane. The two leaflets of a bilayer membrane tend to differ in their lipid composition