Effect of phase transitions on the interaction of peptides and proteins with phospholipids

This review is not a comprehensive study of the broad area of lipid–protein interactions, but rather concentrates on the question of the effect of phase transitions on the interaction of peptides and proteins with phospholipids. Before considering the relative ability of peptides and proteins to incorporate into phospholipid bilayers in the gel or the liquid crystalline state, we briefly review the variety of effects of proteins on lipid phase transitions. It is essential to be cognizant of these effects when discussing how-phase transitions affect protein incorporation. The effect of proteins on lipid order and motion above and below the phase transition is discussed and the current state of knowledge on this topic is briefly reviewed. In discussing the thermodynamics of lipid–protein association and the effect of phase transitions one must deal with systems at equilibrium, a state often difficult to achieve with high molecular weight aggregates. It is demonstrated that there are a variety of effects of phase transitions on protein incorporation. Some proteins incorporate more readily into liquid crystalline state lipid; others incorporate only in a narrow temperature region around the phase transition temperature, while still others interact with lipid over a broad range of temperatures while exhibiting some preference for interacting with gel state lipid. The molecular basis for preferential interaction with gel state lipid is suggested to be the ability of proteins to self-associate, probably at defect sites, below the phase transition temperature and thereby increase protein–protein interactions while maintaining protein–lipid and lipid–lipid interactions. In liquid crystalline state lipid, the protein would be more dispersed, the system would become less stable as a result of decreased protein–protein interactions, and the dispersed protein would also lessen lipid–lipid interactions. The ability of several peptides and proteins to intercalate more readily into gel rather than liquid crystalline state lipid is a more common phenomenon than is generally appreciated.