Molecular dynamics study of the influence of cholesterol on the rigidity of an asymmetric membrane of red blood cells.

Abstract

Analysis of the mechanical properties of the plasma membrane of red blood cell (RBC) is useful for the future exploration of cell-targeted methods for treatment of Alzheimer's disease. This preliminary study aimed to observe the effects cholesterol and lipid concentration/asymmetry have on the membrane rigidity and bilayer thickness. We focused on the structure-property relationship in the plasma membranes via the analysis of bending rigidity as a function of the molar concentration of the cholesterol and lipids in the plasma membrane. The plasma membrane of RBC consists mainly of cholesterol, phosphatidylcholine (PC), sphingomyelin (SM), and proteins. Cholesterol plays a key role in the plasma membrane by maintaining its viscoelasticity and structure via modulating the fluidity and rigidity of the membrane. To analyze these properties, the coarse-grained (CG) molecular dynamics (MD) simulations were performed. The membrane building included cholesterol molar concentration ranging from 10% to 30%. To replicate the asymmetry of the cell SM and PC, the molar concentrations of lipids were varied in the range of 10%-20% and 50%-80%, respectively. The initial membrane configuration was generated using CHARMM-GUI (online graphical user interface tool). The MD simulations were performed with the Gromacs (molecular dynamic simulation program) software using all-atom and coarse-grained approaches. The aggregation of cholesterol at various molar concentrations was observed along with the fluctuation of rigidity, which could be tentatively attributed to the lipid types used in the study, the ratio of cholesterol and lipids, and the use of water as a solvent for both the inner and outer leaflet. In the future we will focus on the all-atom study of the tail interactions between cholesterol and lipids in order to identify the leading factors contributing to the bending rigidity.