Eukaryotic cellular life has an undeniable dependence on cholesterol. Cholesterolcomprises approximately 40 mol % of the lipid portion of the eukaryotic plasma membrane and is generally responsible for the modulation of the physico-chemical properties required for viability and cell proliferation. It is known that cholesterol reduces the passive permeability of membranes, increases membrane mechanical strength, and modulates membrane enzymes.

Among other biological roles it instigates the formation of membrane "rafts", domains where saturated long-chained lipids, cholesterol and specific proteins are concentrated. Rafts distribute proteins and lipids to organelles and the cell surface, activate immune responses, serve as centers for receptor-mediated signal transduction, and are used by many disease-causing bacteria and viruses as a means to populate host cells. The particular contribution cholesterol makes in the formation of rafts is the allowance for maintaining a liquid-ordered, tightly packed membrane domain. The way in which cholesterol achieves this task, however, is not yet known.

In order to understand the physical properties of biological membranes containing cholesterol-induced liquid-ordered phases, studies have been performed on model systems such as monolayers or giant unilamellar vesicles containing binary or ternary mixtures of phospholipids and cholesterol. Different ideas were proposed to explain creation of lipid rafts in these model systems such as existence of specific complexes between cholesterol and phospholipid or umbrella model where cholesterol is shielded from water by neighboring phospholipid or existence of superlattice of cholesterol in membranes. While it is hard to extract the information on the details of molecular interactions from the experiments, computer simulations can be very useful in gaining such information. We use computer simulation techniques to study the interaction between cholesterol and phospholipids that have different headgroups and different tails. We calculate the difference in the free energy of insertion of cholesterol into different membranes and analyze contributions into this free energy. This should provide us with the measure of affinity of cholesterol to a membrane. We also study the possibility of a complexation between cholesterol and phospholipids and the implications of such a possibility on the properties of membranes.