Self-assembly and Equilibration of Bolalipid Membranes Studied by Molecular Dynamics Simulations

Bolalipids are bi-polar lipids, consisting of two mono-polar lipids chemically linked together at either one or both of the lipid tails. Membranes formed by these lipids or by their mixtures with mono-polar lipids are known to have additional mechanical stability while retaining membrane fluidity. This is traditionally attributed to the fact that bolalipids can span the bilayer with their two polar heads positioned at opposite membrane-water interfaces. Our primary interest is to confirm this hypothesis by studying the relation between bolalipid configurations inside the membrane and the structural and mechanical properties of the membrane.To this end, we performed molecular dynamics simulations using the coarse grained MARTINI force field [1]. We start with self-assembly simulations of bolalipids in mixtures with mono-polar lipids, to elucidate the preferred orientation of the bolalipids, i.e. spanning versus a looping configuration in which both head groups reside in the same monolayer. To assure proper equilibration between the spanning and looping conformations, we introduce artificial pores in the membrane to allow lipid flip-flops. We consider different types of linkage, including also bi-polar lipids attached at head group level for which spanning configurations are inaccessible.After equilibration, the membrane properties are characterized in terms of a variety of structural properties and the lateral pressure profile. The resistance of the membrane to mechanical rupture is also investigated. We find that both the spanning/looping ratio and the stability of the membrane depend strongly on the type of crosslink, as well as on the concentration of bolalipids and length of the lipid tails. Our study can help designing new artificial membranes, with higher stability under a variety of extreme conditions.[1] S.J. Marrink, H.J. Risselada, S. Yefimov, D.P. Tieleman, A.H. de Vries, J. Phys. Chem. B 111 (2007) 7812-7824.