Site-specific peroxidation modulates lipid bilayer mechanics
Peroxidation of plasma membranes, characterized by oxidative attack of lipidic carbon–carbon double bonds in unsaturated fatty acids, has been identified as an important biochemical event in multiple pathological conditions, including neurodegenerative diseases, atherosclerosis, diabetes, preeclamp...
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Main Authors: | , , , |
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Format: | Article |
Language: | English |
Published: |
2021
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Subjects: | |
Online Access: | https://hdl.handle.net/10356/153450 |
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Institution: | Nanyang Technological University |
Language: | English |
Summary: | Peroxidation of plasma membranes, characterized by oxidative attack of lipidic carbon–carbon double bonds in unsaturated fatty acids, has been identified as an important biochemical event in multiple
pathological conditions, including neurodegenerative diseases, atherosclerosis, diabetes, preeclampsia,
aging, cancer, etc. Changes to the lipid bilayer structure as a result of lipid peroxidation may lead
to lipid membrane malfunction, and consequently initiate further downstream biochemical cascades.
However, how lipid peroxidation modulates the mechanical properties of lipid membranes remains
largely controversial. In this study, we investigate the peroxidation of lipids with polyunsaturated
fatty acid tails using molecular dynamics simulations. By systematically varying the oxidation site, we
find that lipid peroxidation alters the biophysical properties of bilayer membrane in a peroxidation
site-specific manner. Specifically, our results suggest that 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. Such a peroxidation site-specific modulation of
lipid membrane mechanics provides an explanation for the contradictory results obtained in previous
experiments. Our study paves the way for an improved understanding of the initiation of the
downstream cellular dysfunction caused by lipid peroxidation. |
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