Crystalline Cholesterol: The Material and Its Assembly Lines

Cholesterol is an essential component of animal cell membranes because it influences and controls cell membrane fluidity. Cholesterol is also responsible for the most frequent lethal pathologies in developed countries because of its intimate association with atherosclerotic plaques, the rupture of which may cause heart attacks or strokes. The question is under which conditions cholesterol activity manifests itself, whether in physiology or in pathology. The answer is complex, and there is probably not one certain answer. This review article has its foundations in abundant published knowledge and evidence, but it cannot possibly be comprehensive, because the extent of cholesterol's involvement in chemistry, biology, biophysics, and medicine is so vast that we cannot embrace it all. We review cholesterol as a molecule and in its various crystalline polymorphs. We then examine cholesterol assembly pathways and, finally, cholesterol in biology and in pathology. We propose that cholesterol activity depends on its assembly states in cholesterol crystals or with other lipids in the form of more-or-less organized crystalline domains. In other words, we analyze cholesterol material properties because the assembly state of the cholesterol molecules profoundly affects the properties of the environment in which they reside.