Understanding the Role of Calcium In Membrane Fusion

Thursday, October 20, 2011: 2:25 PM
101 F (Minneapolis Convention Center)
Zeena K. Issa1, Navendu Bhatnagar1, Charles W. Manke1, Bhanu P. Jena1 and Jeffrey J. Potoff2, (1)Chemical Engineering, Wayne State University, Detroit, MI, (2)Chemcial Engineering and Materials Science, Wayne State University, Detroit, MI

Membrane fusion is a localized event which occurs at a sub-millisecond timescale[1] 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[2]. 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.

Extended Abstract: File Not Uploaded
See more of this Session: Thermophysical Properties of Biological Systems II
See more of this Group/Topical: Engineering Sciences and Fundamentals