title: Simulating the Transition between Gel and Liquid-Crystal Phases of Lipid Bilayers: Dependence of the Transition Temperature on the Hydration Level.
abstract: Explicit-solvent molecular dynamics (MD) simulations of the monoglyceride glycerol-1-monopalmitin (GMP; bilayer patch of 2 × 6 × 6 lipids) at different hydration levels (full, half, or quarter hydration) and at different temperatures (318 to 338 K) are reported. The 40 ns simulations (some extended to 200 ns) are initiated from structures appropriate for the gel (GL) or liquid-crystal (LC) phases, with the goal of investigating whether atomistic MD simulations on this time scale can be used to monitor GL ↔ LC transitions in lipid bilayers, and to evaluate the corresponding transition temperatures Tm (as well as the influence of hydration on Tm) in a reliable fashion. The main conclusions are as follows: (i) The GL → LC transition of GMP can be observed on the 40 ns time scale. (ii) The LC → GL transition is comparatively slower, requiring simulations on the 200 ns time scale. (iii) A set of simulations initiated from a structure appropriate for the GL phase and carried out at slightly different temperatures permits the determination of a reliable value for Tm. (iv) The calculated Tm values reproduce the experimentally observed increase in this transition temperature upon decreasing the bilayer hydration. (v) The Tm values calculated at the three hydration levels considered are in essentially quantitative agreement with the experimental phase diagram of GMP. To our knowledge, this study represents the first accurate determination of the Tm of a lipid via atomistic simulations of the (reversible) GL ↔ LC phase transition, as well as the first direct simulation evidence for the increase in the transition temperature upon dehydration. The possible direct determination of Tm and the characterization of environmental effects on this quantity by simulation opens up promising perspectives in the contexts of force field refinement and the investigation of dehydration-induced damages in living cells (and bioprotection by cosolutes).
authors.affiliation: Laboratory of Physical Chemistry, ETH Zürich, CH-8093 Zürich, Switzerland, and University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Bruno A C
authors.initials: BA
authors.lastname: Horta
authors.affiliation: Laboratory of Physical Chemistry, ETH Zürich, CH-8093 Zürich, Switzerland, and University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Alex H
authors.initials: AH
authors.lastname: de Vries
authors.affiliation: Laboratory of Physical Chemistry, ETH Zürich, CH-8093 Zürich, Switzerland, and University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Philippe H
authors.initials: PH
authors.lastname: Hünenberger