Cholesterol affected dynamics of lipids in tailor-made vesicles by ArcVes software during multi micro second coarse grained molecular dynamics simulations

In biotechnology, as well as in nanomedicine, vesicular structures are essential features of the cellular life cycle. Lipid compositions define the applicability of the vesicles. Here, the dynamics of lipid molecules within vesicles of approximately 10 nm in diameter are monitored using coarsegrained molecular dynamics (CGMD) simulations (MARTINI). The vesicles consist of (i) 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), as well as 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), each in a mixture with cholesterol (CHOL) (POPC/CHOL, DOPC/CHOL), (ii) POPC/DOPC mixture and (iii) pure POPC and DOPC. Vesicles are generated by placing the individual lipids spatially separated by an area-per-lipid based distance onto the sphere using an arc correction, implemented into ArcVes, which is an in-house developed software. This protocol leads to the generation of vesicles which remain stable during extended MD simulations. In the presence of cholesterol, the mixed vesicles show time-dependent changes such as a decrease in both radii and membrane thickness. The number of lipids in each leaflet of the mixed vesicles reveals a trend of POPC and DOPC flipping to the outer leaflet and of cholesterol to the inner leaflet. This leads to a cholesterol rich path-formation in both the inner and outer leaflets. The diffusivity of the lipids in the vesicles mixed with cholesterol is lower than the diffusivity of the pure vesicles, similar to the observation for the respective flat membrane patches. In general, the diffusivity of the lipids is larger in the outer leaflets than the inner leaflets.