Molecular dynamics simulation of cation-phospholipid clustering in phospholipid bilayers: possible role in stalk formation during membrane fusion.
In this study, we performed all-atom long-timescale molecular dynamics simulations of phospholipid bilayers incorporating three different proportions of negatively charged lipids in the presence of K(+), Mg(2+), and Ca(2+) ions to systemically determine how membrane properties are affected by cations and lipid compositions. Our simulations revealed that the binding affinity of Ca(2+) ions with lipids is significantly stronger than that of K(+) and Mg(2+) ions, regardless of the composition of the lipid bilayer. The binding of Ca(2+) ions to the lipids resulted in bilayers having smaller lateral areas, greater thicknesses, greater order, and slower rotation of their lipid head groups, relative to those of corresponding K(+)- and Mg(2+)-containing systems. The Ca(2+) ions bind preferentially to the phosphate groups of the lipids. The complexes formed between the cations and the lipids further assembled to form various multiple-cation-centered clusters in the presence of anionic lipids and at higher ionic strength-most notably for Ca(2+). The formation of cation-lipid complexes and clusters dehydrated and neutralized the anionic lipids, creating a more-hydrophobic environment suitable for membrane aggregation. We propose that the formation of Ca(2+)-phospholipid clusters across apposed lipid bilayers can work as a "cation glue" to adhere apposed membranes together, providing an adequate configuration for stalk formation during membrane fusion.
Department of Chemistry, National Central University, Tao-Yuan County, Taiwan. hhtsai@cc.ncu.edu.tw
Hui-Hsu Gavin
HH
Tsai
Wei-Xiang
WX
Lai
Hong-Da
HD
Lin
Jian-Bin
JB
Lee
Wei-Fu
WF
Juang
Wen-Hsin
WH
Tseng
D002412:Cations / Q000737:chemistry*; D008051:Lipid Bilayers; D008561:Membrane Fusion; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010743:Phospholipids / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D002412:Cations; D008051:Lipid Bilayers; D010743:Phospholipids; D014867:Water