(A-37) Lipid Peroxidation-induced Membrane Mechanics Modulation and Shape Transformation of Nanoliposomes

Introduction:: Plasma membranes form the physical barrier that separates the intracellular contents from the extracellular environments and are essential to the homeostasis of the cell. It has been identified that lipid peroxidation is associated with multiple pathological conditions, including neurodegenerative diseases, atherosclerosis, diabetes, preeclampsia, aging, cancer, etc. However, how exactly lipid peroxidation contributes to those pathological conditions remains largely elusive. Especially, contradictory results regarding its regulation of membrane properties have been reported in experiments.

Materials and Methods:: In this study, we first performed molecular dynamics simulations to systematically investigate how lipid peroxidation modulates the structural and mechanical properties of planar lipid membranes. We then extended our simulation systems to nanosized lipid vesicles to interrogate how the change in membrane mechanics caused by lipid peroxidation might alter the vesicle shape.

Results, Conclusions, and Discussions:: Our simulations reveal that lipid peroxidation modulates lipid bilayer mechanics in a peroxidation site-specific manner: peroxidation at sites in the bilayer interior disturbs and softens the membrane, whereas peroxidation at sites near the membrane-water interface results in a more ordered and stiffer membrane. Interestingly, we find that the increase in the area per lipid as a result of lipid peroxidation at sites in the bilayer interior leads to a dramatic shape transformation of nanosized vesicles from spherical to prolate. Our finding is essential to a more accurate understanding of the initiation of any lipid peroxidation-induced downstream biochemical events in various pathological conditions. In addition, the lipid peroxidation-induced vesicle shape transformation suggests a novel way to fabricate non-spherical nanoliposomes that may serve as a more efficient drug delivery system.

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