Lateral pressure in lipid membranes and its role in function of membrane proteins

Abstract

A very important component of cells is the cell membrane separating the contents of a cell from the outside world. The cell membrane contains membrane proteins which, for example, regulate permeation of molecules through the cell membrane. This regulation is essential for functions of cells. Meanwhile, increasing experimental evidence shows that there is a connection between physical properties of the cell membrane and membrane protein functionality. However, this connection is not fully understood. One hyphothesis is that the so-called lateral pressure profile arising from the inhomogeneous nature of a lipid bilayer would regulate membrane protein functionality. The main difficulties in testing this hyphothesis are that experimental measurements of the lateral pressure and the cross sectional area profiles are very difficult to carry out. This issue is considered in this thesis by calculating theoretical lateral pressure profiles of lipid bilayers, using data obtained via molecular dynamics simulations. The results are then compared to available experimental data. The insight gained in this manner is used to make predictions for membrane protein functionality. The results presented in this thesis suggest that the theoretical pressure profiles are in relatively good agreement with the available experimental results, and that changes in lipid composition can have a major effect on the pressure profile of a lipid bilayer. What is more, the results suggest that these changes have a significant influence on membrane protein functionality. We also show that the shape of a protein embedded in a membrane, especially in the interfacial region between hydrophobic and hydrophilic regions, is a very important player in gating of mechanosensitive channels.