Impact of Lipid Peroxidation on the Response of Cell Membranes to High-Speed Equibiaxial Stretching: A Computational Study

Abstract

The difference between diseased and healthy cellular membranes in response to mechanical stresses is crucial for biology, as well as in the development of medical devices. However, the biomolecular mechanisms by which mechanical stresses interact with diseased cellular components remain largely unknown. In this work, we focus on the response of diseased cellular membranes with lipid peroxidation to high-speed tensile loadings. We find that the critical areal strain (ξc, when the pore forms) is highly sensitive to lipid peroxidation. For example, ξc of a fully oxidized bilayer is only 64 and 69% of the nonoxidized one at the stretching speed of 0.1 and 0.6 m/s, respectively. ξc decreases with the increase in the oxidized lipid ratio, regardless of the speeds. Also, the critical rupture tension of membranes exhibits a similar change. It is obvious that the oxidized membranes are more easily damaged than normal ones by high-speed stretching, which coincides with experimental findings. The reason is that peroxidation introduces a polar group to the tail of lipids, increases the hydrophilicity of tails, and warps the tails to the membrane–water interface, which causes loose accumulation and disorder of lipid tails. This can be deduced from the variation in the area per lipid and order parameter. In addition, the lowering stretching modulus and line tension of membranes (i.e., softening) after lipid peroxidation is also a significant factor. We reveal the difference between the peroxidized (diseased) and normal membrane in response to high-speed stretching, give the ξc value in the pore formation of membranes and analyze the influence of the stretching speed, peroxidation ratio, and molecular structure of phospholipids. We hope that the molecular-level information will be useful for the development of biological and medical devices in the future