A comprehensive study of cholesterol in biomembranes using computer simulations
Several methods were applied to study the effects of cholesterol on multi-component lipid bilayers. The goal is to investigate the validity of the "Umbrella Effect" via simulations and experiments. The Umbrella Model is a hypothesis proposed based on previous structural and thermodynamical studies of lipid membranes containing cholesterol. DPPC is the most widely studied phospholipid in the simulation community. It has a large polar headgroup (which consists of a positively charged choline group and a negatively charged phosphate group), a glycerol group and two long saturated hydrocarbon chains. On the other hand, cholesterol has a relatively large carbon-ring body, compared to its small hydrophilic hydroxyl group. When a binary mixture of DPPC/cholesterol is placed in an aqueous environment, it has been suggested that cholesterol is always trying to find a “shield” to protect it from extensive contact with water, and this shield is most likely to be provided by the headgroups of phospholipids. This hypothesis is termed the “Umbrella Model”. Monte Carlo (MC) simulations will be used to study the phase transitions of multi-component lipid mixtures and molecular dynamics (MD) simulations will be used to test the Umbrella Model in direct and indirect ways, and to interpret the experimental data. Melittin is the most studied antimicrobial peptide, it can cause cell death by damaging cell membranes. Melittin interacts differently with various membrane components, such as cholesterol and negatively-charged phospholipid, both of which have been shown to reduce melittin's lytic effect against the membrane. Several model systems were constructed and simulated, different effects were observed and the possible mechanisms were discussed.