Probing Cholesterol Dependent Lipid Properties Using Molecular Dynamics Simulations of BODIPY-PC in Explicit DMPC and DPPC Membranes

Abstract

Dunn and co-workers have used polarized total internal reflection fluorescence microscopy to measure the tilt angle of a single molecule (BODIPY-PC) relative to the membrane normal to characterize the membrane properties. Recently, they found that increasing quantities of cholesterol in monolayer and bilayer membrane systems leads to a much smaller tilt angle of the BODIPY-PC molecule. To better understand the influence of cholesterol on membrane properties and its relation to BODIPY-PC tilting, we have performed molecular dynamics (MD) simulations of BODIPY-PC in explicit dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphocholine (DMPC) monolayer and bilayer membrane systems with systematically increasing concentrations of cholesterol (0, 5, 10, 15, 20, 33, 50%). After 4 ns of equilibration, each system has been simulated for another 16 ns. Preliminary results indicate that the BODIPY-PC tilt angle decreases as a function of increasing cholesterol concentration until 10% cholesterol after which there appears to be cholesterol saturation and the rigidifying affect ceases. Other points of interest include confirming the applicability of monolayer data for bilayer systems and explaining any quantifiable differences between the DPPC and DMPC membrane systems. We will present the orientation (azimuthal and rotational angle distribution) of BODIPY-PC, the BODIPY-PC tilting energetics, various membrane properties, and the spatial distribution of the cholesterol as a function of cholesterol concentration.