Stability of Asymmetric Lipid Bilayers Assessed by Molecular Dynamics Simulations Export

@article{citeulike:6002853, abstract = {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 diC8PC 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.}, author = {Esteban-Martín, Santi and Risselada, H. Jelger and Salgado, Jesús and Marrink, Siewert J.}, citeulike-article-id = {6002853}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ja904450t}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ja904450t}, day = {28}, doi = {10.1021/ja904450t}, journal = {Journal of the American Chemical Society}, keywords = {biomembranes, molecular\_simulation}, month = {October}, number = {42}, pages = {15194--15202}, posted-at = {2009-10-24 22:43:14}, priority = {2}, title = {Stability of Asymmetric Lipid Bilayers Assessed by Molecular Dynamics Simulations}, url = {http://dx.doi.org/10.1021/ja904450t}, volume = {131}, year = {2009} }

TY - JOUR ID - citeulike:6002853 L3 - citeulike-article-id:6002853 N2 - 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 diC8PC 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. IS - 42 JF - Journal of the American Chemical Society EP - 15202 TI - Stability of Asymmetric Lipid Bilayers Assessed by Molecular Dynamics Simulations VL - 131 SP - 15194 KW - biomembranes KW - molecular_simulation AU - Esteban-Martín, Santi AU - Risselada, Jelger AU - Salgado, Jesús AU - Marrink, Siewert PY - 2009/10/28/ UR - http://dx.doi.org/10.1021/ja904450t ER -