Amphiphile orientation: physical chemistry and biological function

The critical role that amphiphiles play in biology is to provide an orienting force, probably the single most important force for structural organization in living matter. It is responsible for the organization of biological lipids into the membranes that define a living cell and prevent mixing of intracellular contents with the inanimate outside world. The same force, much reduced in magnitude, is responsible for the folding of protein polypeptide chains to specific three-dimensional structures, thereby creating the multitude of enzymes of the living cell, and the proteins that traverse the cell membrane for communication between inside and outside. Study of these phenomena has a long and fascinating history, but many important questions--all at the interface between biological and physical chemistry--remain unanswered. What is the mechanism of vesiculation of phospholipid bilayers? What is the functional role of cholesterol in cell membranes? Knowing that molecular clusters are important elements in the structure of liquid water, how do we explain the smooth extrapolation of thermodynamic data from very large to very small hydrophobic interfacial areas?