Effect of Lipid Structure and Material Properties on the Membrane Stability to Pore Formation

Abstract

Biological membranes are natural barriers that preserve the integrity of the cell and its organelles. Even temporary damage of the cell membrane can break its normal homeostasis that will start the recovery mechanisms, apoptosis and inflammatory reactions. Formation of pores, through defects, in the lipid bilayer of biological membranes can lead to serious disruption of the normal lifecycle of the cells and the development of pathologies.A two-pronged approach was used to study the energetics of pore formation in lipid membranes assembled by isoprenoid lipids (e.g., DPhPC and Di-O-PhPC). The first prong studied the line tension of DPhPC, Di-O-PhPC, DOPC, and POPC using MD simulations and experiments with an electrical breakdown technique. Resistance to pore formation can be characterized by pore edge line tension, which describes the energy barrier height that should be overcome to irreversibly expand the pore, i.e. to rupture the membrane. A method of measuring pore line tension in MD, determining the lateral tension of the lipid membrane with the static pore, and experiments revealed that branched lipid significantly increased the pore energy and membrane resistance to pore formation. Additionally, work on GUVs and MD showed that low-weight solvent significantly lowers pore edge energy. The second prong used MD to quantify other key material properties that can affect pore formation (i.e., the compressibility modulus, bending modulus, per area free energy change with respect to curvature, and the intrinsic curvature). DPhPC's bending modulus is about half that of DPPC, but DPhPC's compressibility modulus is about two times larger than DPPC. Finally, DPhPC's effect on monolayer spontaneous curvature is similar to that of a PE lipid. Thus both structural peculiarities of lipid tails and solvents strongly influence membrane stability.