Membrane fusion is a localized event which occurs at a sub-millisecond timescale when two distinct lipid bilayers fuse with each other, subsequently opening a channel and allowing the transfer of contents. This process is a critical step in a variety of cellular functions, including exocytosis, fertilization, and neurotransmitter release. The process of membrane fusion is thermodynamically unfavorable, and several factors are required to overcome the activation energy barrier[3,4]. Ca2+ has been identified as one such factor that regulates membrane fusion, although the precise mechanism through which Ca2+ triggers membrane fusion remains unclear [5-7].
This work is focused on understanding the role of Ca2+ in the fusion process at the atomic level. Using molecular dynamics simulations and a variety of techniques such as adaptive force bias and steered molecular dynamics, the interactions of Ca2+, Mg2+ and Ba2+ with phospholipid bilayers, and the membrane fusion protein snaptotagamin (SYT) are studied. These simulations show Ca2+ has the unique ability to bridge apposed phospholipid head groups, while Mg2+ and Ba2+ do not. Potential of mean force calculations are used to show this propensity for Ca2+ to bridge opposed bilayers is due to an optimum balance of Ca2+-phospholipid and Ca2+ water interactions. The effect of cation binding to phospholipid head groups on the local structure of water and the free energy barriers to phospholipid rearrangement are discussed.
1. Llinas, R.; Steinberg, I. Z.; Walton, K. Biophys. J. (1981), 33, 323.
2. Jahn, R.; Sudhoff, T. C. Annu. Rev. Biochem. (1999), 68, 863.
3. Rand, R. P.; Parsegian, V. A. Biochim. Biophys. Acta (1989), 988, 351.
4. Kinnunen, P. K. J.; Holopainen, J. M. Biosc. Rep. (2000), 20, 465.
5. Papahadjopoulos, D.; Poste, Schaeffer, B. E.; Vail, W. J. Biochim. Biophys. Acta (1974), 352, 10.
6. Papahadjopoulos, D; Nir, S.; Bizgunes, N. J. Bioenerg. Biomembr. (1990), 22, 157.
7. Portis, A.; Newton, C.; Pangborn, W.; Papahadjopoulos, D. Biochemistry (1979), 18, 780.
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