Stability of Asymmetric Lipid Bilayers Assessed by Molecular Dynamics Simulations

被引:70
作者
Esteban-Martin, Santi [3 ]
Risselada, H. Jelger [1 ,2 ]
Salgado, Jesus [3 ]
Marrink, Siewert J. [1 ,2 ]
机构
[1] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, NL-9700 AB Groningen, Netherlands
[2] Univ Groningen, Zernike Inst Adv Mat, NL-9700 AB Groningen, Netherlands
[3] Univ Valencia, Inst Ciencias Mol, Valencia 46980, Spain
关键词
COARSE-GRAINED MODEL; MECHANOSENSITIVE CHANNEL; PORE FORMATION; EGG PHOSPHATIDYLCHOLINE; ANTIMICROBIAL PEPTIDES; MEMBRANE; PRESSURE; SOLUBILIZATION; TRANSITION; MECHANISM;
D O I
10.1021/ja904450t
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The asymmetric insertion of amphiphiles into biological membranes compromises the balance between the inner and outer monolayers. As a result, area expansion of the receiving leaflet and curvature strain may lead to membrane permeation, shape changes, or membrane fusion events. We have conducted both atomistic and coarse-grained molecular dynamics simulations of dipalmitoyl-phosphatidylcholine (DPPC) bilayers to study the effect of an asymmetric distribution of lipids between the two monolayers on membrane stability. Highly asymmetric lipid bilayers were found to be surprisingly stable within the submicrosecond time span of the simulations. Even the limiting case of a monolayer immersed in water ruptured spontaneously only after at least 20 ns simulation. A thermal shock could destabilize these kinetically trapped states. We also studied mixed systems composed of DPPC and short tail diC(8)PC lipids, showing that the presence of the cone-shaped short tail lipid facilitates the release of tension in the asymmetric systems via formation of a transmembrane pore. Thus, asymmetric area expansion and curvature stress cooperate to yield bilayer disruption. It appears that, although asymmetric area expansion destabilizes the bilayer structure, the activation energy for transmonolayer lipid re-equilibration is increased. Such a large kinetic barrier can be reduced by lipids with positive spontaneous curvature. These effects are important at the onset of bilayer destabilization phenomena, such as lipid pore formation and membrane fusion, and should be considered for the mechanism of induction of such processes by peptides and proteins.
引用
收藏
页码:15194 / 15202
页数:9
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