This research aims to combine tools for characterizing the high-resolution structures of cell membranes, with advanced atomistic and statistical computer modeling, to determine the role of calcium ions in the membrane fusion process. The main hypothesis of the proposal is that the presence of calcium ions can reduce electrostatic repulsion between opposing bilayers by bridging the phospholipid headgroups of the opposing outer membrane layers and, therefore, promoting membrane fusion. The project will use both simulations and experiments in real lipid membranes in the form of liposomes. The specific aims are: (1) determination of possible interactions between hydrated calcium ions and phospholipid headgroups of opposing bilayer membranes and also between phospholipids headgroups on the same membrane, (2) evaluation of the alterations between opposing bilayers that are caused by the presence of calcium cations, (3) evaluation of the role of calcium cations on the binding interactions between membrane associated proteins (t-/v-SNAREs), and (4) to provide undergraduate and graduate research experience for students. The process of cell fusion is very important to normal cellular function, and to abnormal cell events, such as drug delivery (a good thing) or pathogen attack (a bad thing). Understanding the precise role of calcium ions in this mechanism would, therefore, be of great benefit to a broad range of fundamental and practical matters. Undergraduate and graduate students will be involved.
