We present an improved and extended version of our coarse grained lipid model. The new version, coined the MARTINI force field, is parametrized in a systematic way, based on the reproduction of partitioning free energies between polar and apolar phases of a large number of chemical compounds. To reproduce the free energies of these chemical building blocks, the number of possible interaction levels of the coarse-grained sites has increased compared to those of the previous model. Application of the new model to lipid bilayers shows an improved behavior in terms of the stress profile across the bilayer and the tendency to form pores. An extension of the force field now also allows the simulation of planar (ring) compounds, including sterols. Application to a bilayer/cholesterol system at various concentrations shows the typical cholesterol condensation effect similar to that observed in all atom representations.

/pdf/the-martini-force-field-coarse-grained-model-for-3l11ncr3fg.pdf

The MARTINI force field : Coarse grained model for biomolecular simulations

This paper describes the parametrization of a new coarse grained (CG) model for lipid and surfactant systems. Reduction of the number of degrees of freedom together with the use of short range potentials makes it computationally very efficient. Compared to atomistic models a gain of 3-4 orders of magnitude can be achieved. Micrometer length scales or millisecond time scales are therefore within reach. To encourage applications, the model is kept very simple. Only a small number of coarse grained atom types are defined, which interact using a few discrete levels of interaction. Despite the computational speed and the simplistic nature of the model, it proves to be both versatile in its applications and accurate in its predictions. We show that densities of liquid alkanes from decane up to eicosane can be reproduced to within 5%, and the mutual solubilities of alkanes in water and water in alkanes can be reproduced within 0.5 kT of the experimental values. The CG model for dipalmitoylphosphatidylcholine (DPPC) is shown to aggregate spontaneously into a bilayer. Structural properties such as the area per headgroup and the phosphate-phosphate distance match the experimentally measured quantities closely. The same is true for elastic properties such as the bending modulus and the area compressibility, and dynamic properties such as the lipid lateral diffusion coefficient and the water permeation rate. The distribution of the individual lipid components along the bilayer normal is very similar to distributions obtained from atomistic simulations. Phospholipids with different headgroup (ethanolamine) or different tail lengths (lauroyl, stearoyl) or unsaturated tails (oleoyl) can also be modeled with the CG force field. The experimental area per headgroup can be reproduced for most lipids within 0.02 nm(2). Finally, the CG model is applied to nonbilayer phases. Dodecylphosphocholine (DPC) aggregates into small micelles that are structurally very similar to ones modeled atomistically, and DOPE forms an inverted hexagonal phase with structural parameters in agreement with experimental data.

/pdf/coarse-grained-model-for-semiquantitative-lipid-simulations-3235leilrn.pdf

Coarse grained model for semiquantitative lipid simulations

Understanding and controlling the interaction of graphene-based materials with cell membranes is key to the development of graphene-enabled biomedical technologies and to the management of graphene health and safety issues. Very little is known about the fundamental behavior of cell membranes exposed to ultrathin 2D synthetic materials. Here we investigate the interactions of graphene and few-layer graphene (FLG) microsheets with three cell types and with model lipid bilayers by combining coarse-grained molecular dynamics (MD), all-atom MD, analytical modeling, confocal fluorescence imaging, and electron microscopic imaging. The imaging experiments show edge-first uptake and complete internalization for a range of FLG samples of 0.5- to 10-μm lateral dimension. In contrast, the simulations show large energy barriers relative to kBT for membrane penetration by model graphene or FLG microsheets of similar size. More detailed simulations resolve this paradox by showing that entry is initiated at corners or asperities that are abundant along the irregular edges of fabricated graphene materials. Local piercing by these sharp protrusions initiates membrane propagation along the extended graphene edge and thus avoids the high energy barrier calculated in simple idealized MD simulations. We propose that this mechanism allows cellular uptake of even large multilayer sheets of micrometer-scale lateral dimension, which is consistent with our multimodal bioimaging results for primary human keratinocytes, human lung epithelial cells, and murine macrophages.

https://www.pnas.org/content/pnas/110/30/12295.full.pdf

Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sites

Lipids on the move: simulations of membrane pores, domains, stalks and curves.

Molecular dynamics simulations of pore formation and mem-brane rupture in phospholipid bilayers under mechanical andelectrical stress at an atomic level are presented. Pore formationcan be induced on a nanosecond time scale in simulations wherethe lateral pressure exceeds -200 bar or where an electric field of0.5 V/nm is applied across the membrane.Lipid bilayer membranes are remarkable structures consistingof two leaflets of phospholipids. Their mechanical properties arecentral to understanding the behavior of cell membranes. Forexample, the formation of transient water pores is believed tounderlie the passive transport of protons and hydrophilic compoundsthrough the bilayer. Pore formation is also relevant during processessuch as cell fusion and is important for drug release from liposomes.Experimentally, pores can be induced in membranes by applyingmechanical stress (i.e., pipet aspiration experiments) or an electricfield (electroporation). The precise mechanism by which pores formand their size, structure, and stability are, however, poorlyunderstood.

/pdf/simulation-of-pore-formation-in-lipid-bilayers-by-mechanical-j7oqyywb8r.pdf

Simulation of pore formation in lipid bilayers by mechanical stress and electric fields

https://www.cell.com/biophysj/pdf/S0006-3495(01)75737-2.pdf

K.L. Rabone

Papers

Mesoscopic Simulation of Cell Membrane Damage, Morphology Change and Rupture by Nonionic Surfactants