ABSTRACT

Inverted Phase Transition Mechanisms............................... 62 4.3 Using Lipid Phase Behavior to Study

Membrane Fusion................................................................... 70 4.3.1 Ways in Which Exogenous Additives Move

Lamellar/Inverted Phase Boundaries: Effects of Lipid Additives ....................................................... 70 4.3.1.1 Spontaneous Curvature .............................. 71 4.3.1.2 Chain-Packing Energy ................................ 72

4.3.2 Effects of Peptides and Enzymes on Inverted Phase Behavior and Fusion....................................... 73 4.3.2.1 Enzymatic Production of Lipids that

Change Spontaneous Curvature and Chain-Packing Energy of Membrane Lipids............................................................ 74

4.3.2.2 Effects of Viral Fusion Peptides................. 75 4.3.2.3 Membrane-Spanning Peptides.................... 78

4.4 Studying Lamellar/Q

Phase Transitions to Refine Models of Fusion Intermediate Energetics .......................... 84 4.4.1 Evaluation of the Gaussian Curvature Elastic

Coefficient by Measurement of T

............................. 85 4.4.2 Implications for Membrane Fusion........................... 87 4.4.3 Implications for the Effects of Peptides on

Membrane Fusion and Q

Phase Formation ........... 88 4.5 Conclusion............................................................................... 89 References......................................................................................... 90

Membrane fusion is the process by which two closed lipid membrane vesicles form a single, larger vesicle. The aqueous contents and the membranes of the two original vesicles mix, and no significant leakage of the contents to the suspending medium occurs. Fusion is a ubiquitous process in biology. It is a necessary step in many critical functions in single cells (e.g., exocytosis, vesicular transport), in multicellular organisms (e.g., fertilization, immuno-and neurosecretion), and viral infection. The process is of intense biomedical interest and is the basis of some drug delivery systems. The purpose of this chapter is to review the ways in which studies of inverted cubic (Q

) phase behavior help us understand the mechanism of this biological process.