Mesoscopic models of biological membranes

Abstract

Phospholipids are the main components of biological membranes and dissolved in water these molecules self-assemble into closed structures, of which bilayers are the most relevant from a biological point of view. Lipid bilayers are often used, both in experimental and by theoretical investigations, as model systems to understand the fundamental properties of biomembranes. The properties of lipid bilayers can be studied at different time and length scales. For some properties it is sufficient to envision a membrane as an elastic sheet, while for others it is important to take into account the details of the individual atoms. In this review, we focus on an intermediate level, where groups of atoms are lumped into pseudo-particles to arrive at a coarse-grained, or mesoscopic, description of a bilayer, which is subsequently studied using molecular simulation.The aim of this review is to compare various strategies to coarse grain a biological membrane. The conclusion of this comparison is that there can be many valid different strategies, but that the results obtained by the various mesoscopic models are surprisingly consistent. A second objective of this review is to illustrate how mesoscopic models can be used to obtain a better understanding of experimental systems. The advantage of coarse-grained models is that these can be simulated very efficiently, so that phenomena involving large systems, or requiring a large number of simulations, can be studied in detail. This is illustrated with the study of the relation between the phase behavior of a membrane and the structure of the phospholipids, and the membrane structural changes due to molecules (such as alcohols, cholesterol and anesthetics) adsorbed to the membrane. We then discuss the effect of transmembrane peptides on the local structure of a membrane and the mechanism of vesicle fusion and fission.

Organization, dynamics, and segregation of Ras nanoclusters in membrane domains

“…Therefore, the use of fully atomistic methods is impractical. A number of CG models have been proposed to overcome this challenge (19)(20)(21)(22)(23). The MARTINI CG model (19,20) used here (Fig.…”

An implicit solvent coarse-grained lipid model with correct stress profile

“…Perhaps the disagreement arises from known simulation artifacts in the calculation of the pressure tensor for "soft" mesoscale models, or possibly due to the integration error that accumulates from an ill-defined time step. 33 Efficient DPD simulations have reproduced a qualitatively correct stress profile; in a review of membrane models, Venturoli et al 17 reproduce a stress profile that has the same features as the all-atom simulation. Finally, detailed explicit solvent coarse-grained simulations, such as the MARTINI forcefield 19 and a LJ/GayBerne lipid model, 60 nicely reproduce all-atom stress profiles.…”

“…Even so, the membrane bilayers themselves also assemble and are stabilized by a surrounding aqueous environment, requiring a decision in the coarse-graining process for lipid chemistry as to whether the solvent environment will be implicitly or explicitly described. 16 The successes of explicit solvent coarse-grained lipid models have been recently reviewed by Venturoli et al 17 Coarse-graining strategies such as that used in the MARTINI model 18,19 seek to retain many of the same features of the all-atom solvent and lipid models such as explicit Coulomb forces. It has been used to study protein insertion and assembly in the bilayer, as well as the properties of lipid mixtures including the addition of cholesterol, to name a few applications.…”

Multiscale modeling of emergent materials: biological and soft matter

“…193 that extends DPD-VV to allow DPD simulation to be performed in both constant pressure and constant surface tension, which has allowed for the simulation of biological membranes using DPD. 194 Thermostating also remains an active field, and the latest addition is the robust ''extended DPD thermostat'' by Junghans et al 195 4 Analytical approaches: regarding a systematic derivation of DPD. The standard DPD with soft potentials as presented above is phenomenological.…”