Lipid phase behavior and stabilization of domains in membranes of platelets.

Lipid domains are acquiring increasing importance in our understanding of the regulation of several key functions in living cells. We present here a discussion of the physical mechanisms driving the phase separation of membrane lipid components that make up these domains, including phase behavior of the lipids and the role of cholesterol. In addition, we discuss phenomena that regulate domain geometry and dimensions. We present evidence that these mechanisms apply to the regulation of domains in intact cells. For example, the observation that physiologically functional microdomains present at 37 degrees C aggregate into macrodomains in human blood platelets when they are chilled below membrane lipid phase transition temperatures is predictable from the known behavior of the constituent lipids in vitro. Finally, we show that the principles developed from studies on these lipids in model systems can be used to develop techniques to stabilize the physiological, resting microdomain structure of platelets during freeze-drying. These latter findings have immediate applications in clinical medicine for the development of methods for storing platelets for therapeutic use.