Membrane Cholesterol in Cataract and Atherosclerosis: EPR Spin-Labeling Approaches
Cholesterol is the major lipid of the animal cell membranes. It is mainly located in plasma membranes where the cholesterol/phospholipid molar ratio is typically from 0.5 to 1. In human lens fiber-cells this ratio can be as high as 2 and even 4. At high-saturating and over-saturating cholesterol content, pure cholesterol bilayer domains (CBDs) are formed in model and biological membranes. CBDs are surrounded by a bulk phospholipid bilayer saturated with cholesterol. Formation of CBDs precedes formation of cholesterol crystals, and it is likely that CBDs are precursors of monohydrate cholesterol crystals. Only in the eye lens do CBDs – the integral part of the aged fiber-cell membrane – play a positive physiological role, helping to maintain lens transparency to visible light, and therefore possibly preventing cataract formation. In other organs and tissues, appearance of these domains is usually a sign of pathology. A better understanding of physiological functions of CBDs and cholesterol crystals in different organs and tissues requires increased understanding of cholesterol functions on a molecular level, including mechanisms of the formation of cholesterol-induced phases and domains in phospholipid membranes, as well as characterization of these phases and domains. Our results based on electron paramagnetic resonance (EPR) spin-labeling experiments with lens-lipid membranes, have allowed us to identify the significant functions of cholesterol specific to the fiber-cell plasma membrane, which are manifest through cholesterol-membrane interactions. These results emphasize the positive physiological functions of high cholesterol contents. However, participation of membrane high cholesterol in pathological processes (for example in development of atherosclerosis) needs better understanding on biophysical (molecular) level.