Membrane Fusion

 

fusionMembrane fusion lies at the heart of important biological processes. In vivo, membrane fusion is tightly regulated by proteins. The basic mechanism, however, is primarily determined by the physics of lipid-lipid interactions.
 
 

We have used the Martini model to provide insight into the molecular details of fusion, either between planar lipid membranes [2,4] or between small vesicles [1]. Depending on lipid composition, the rate of fusion might vary by orders of magnitude, and the system can be trapped at any of the intermediate stages of fusion such as the stalk or the hemifusion state. The effect of peptides on the fusion process can also be studied; for instance, we found that [3,8] fusion peptides stabilize a stalk/pore complex, an important intermediate of the fusion pathway, as depicted in the figure. Most recently the fusion of vesicles mediated by lung surfactant protein B [5] and the SNARE complex [6] have been simulated with Martini ! For a recent review of simulations on fusion, including  many Martini-based works, see [7].

 

  • [1] S.J. Marrink, A.E. Mark. The mechanism of vesicle fusion as revealed by molecular dynamics simulations. JACS, 125:11144-11145, 2003.
  • [2] S.J. Marrink, A.E. Mark. Molecular view of hexagonal phase formation in phospholipid membranes. Biophys. J., 87:3894-3900, 2004.
  • [3] M. Fuhrmans, V. Knecht, S.J. Marrink. A single bicontinuous cubic phase induced by fusion peptides. JACS, 131:9166-9167, 2009.
  • [4] Y.G. Smirnova, S.J. Marrink, R. Lipowsky, V. Knecht. Solvent-exposed tails as prestalk transition states for membrane fusion at low hydration. JACS, 132:6710-6718, 2010.
  • [5] S. Baoukina, D.P. Tieleman. Direct simulation of protein-mediated vesicle fusion: lung surfactant protein B. Biophys. J., 99:2134-2142, 2010.
  • [6] H.J. Risselada, C. Kutzner, H. Grubmüller. Caught in the act: Visualization of SNARE-mediated fusion events in molecular detail. ChemBioChem, 12, 2011.
  • [7] A.J. Markvoort, S.J. Marrink. Lipid acrobatics in the membrane fusion arena, In Curr. Top. Membr. in Membrane Fusion, Vol. 68, L.V. Chernomordik, M.M. Kozlov Eds. Elsevier, New York, NY, pp. 259-294, 2011. abstract, reprint
  • [8] M. Fuhrmans, S.J. Marrink. Molecular view of the role of fusion peptides in promoting positive membrane curvature. JACS, 134:1543–1552, 2012. abstract