Large-scale simulation of biomembranes incorporating realistic kinetics into coarse-grained models

Abstract

Biomembranes are two-dimensional assemblies of phospholipids that are only a few nanometres thick, but form micrometre-sized structures vital to cellular function. Explicit molecular modelling of biologically relevant membrane systems is computationally expensive due to the large number of solvent particles and slow membrane kinetics. Coarse-grained solventfree membrane models offer efficient sampling but sacrifice realistic kinetics, thereby limiting the ability to predict pathways and mechanisms of membrane processes. Here, we present a framework for integrating coarse-grained membrane models with continuum-based hydrodynamics. This framework facilitates efficient simulation of large biomembrane systems with large timesteps, while achieving realistic equilibrium and non-equilibrium kinetics. It helps to bridge between the nanometer/nanosecond spatiotemporal resolutions of coarse-grained models and biologically relevant time-and lengthscales. As a demonstration, we investigate fluctuations of red blood cells, with varying cytoplasmic viscosities, in 150-milliseconds-long trajectories, and compare kinetic properties against single-cell experimental observations.

Thermodynamics and kinetics of aggregation of flexible peripheral membrane proteins

“…In order to predict realistic timescales and mechanisms, the model must faithfully capture the kinetics for the membrane and membrane-bound proteins. We have previously done that for the kinetics of out-of-plane membrane fluctuations with the current model [39]. Focusing on the in-plane kinetics, here we investigate the in-plane diffusion of protein-bound particles (Fig.…”

“…The model is fully particle-based so as to facilitate the integration with particle-based simulations of cellular kinetics [31,32], and particularly with interacting-particle reaction dynamics (iPRD) [33][34][35][36]. Our model builds on a previous coarse-grained particlebased membrane model mimicking the mechanics of the bilayer, while coupling to the hydrodynamics of the solvent to reproduce realistic large-scale equilibrium and non-equilibrium kinetics [37][38][39]. This model is extended to incorporate cooperative membrane-mediated interactions as well as the dynamics of protein aggregation, in order to arrive at a realistic model of the dynamic membrane-protein interplay.…”

Quantitative analysis of membrane-mediated interactions and aggregation of flexible peripheral proteins orchestrating large-scale membrane remodeling

“…We have considered hydrodynamic coupling to an aqueous solvent with the viscosity of η = 0.890 mPa s, and have included hydrodynamic interactions between nearest-neighbor particles (the "Hydro NN" model described in ref. [39]). All simulations have been carried out at the biological temperature of T = 310 K. We have coupled the in-plane degrees of freedom to the Langevin piston barostat to simulate tensionless membranes [62].…”

Three-dimensional morphodynamics simulations of macropinocytic cups

“…22.165027 doi: bioRxiv preprint which allows one to simulate interfaces with complex geometry such as growing crystals (33,34), vesicle coarsening or fission (35) as well as an overall shape of migratory cells (18,20,25,27). The phase-field approach allows one to compute cellular membrane deformation on the order of micrometers in spatial scale and seconds to minutes in timescales, which is in contrast to nanometer-scale models that describe microsecond order phenomena (36). Here, an abstract field variable is introduced to describe the cell interior region = 1 and the exterior region and = 0 (Fig.…”