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...

Full description

Saved in:
Bibliographic Details
Main Authors: Chng, Choon-Peng, Sadovsky, Yoel, Hsia, K. Jimmy, Huang, Changjin
Other Authors: School of Mechanical and Aerospace Engineering
Format: Article
Language:English
Published: 2021
Subjects:
Online Access:https://hdl.handle.net/10356/153450
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-153450
record_format dspace
spelling sg-ntu-dr.10356-1534502023-03-04T17:24:21Z Site-specific peroxidation modulates lipid bilayer mechanics Chng, Choon-Peng Sadovsky, Yoel Hsia, K. Jimmy Huang, Changjin School of Mechanical and Aerospace Engineering School of Chemical and Biomedical Engineering Magee-Womens Research Institute Science::Physics::Descriptive and experimental mechanics Science::Biological sciences::Biophysics Lipid Peroxidation Molecular Simulation 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. Ministry of Education (MOE) Nanyang Technological University Accepted version Y.S., K.J.H. and C.H. acknowledge the financial support by the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD086325). K.J.H. would like to acknowledge financial support from Nanyang Technological University (start-up grant M4082428.050). C.H. would also like to acknowledge financial support from Nanyang Technological University (start-up grant M4082352.050) and the Ministry of Education, Singapore, under its Academic Research Fund Tier 1 (M4012229.050). The computational work for this article was fully performed on resources of the National Supercomputing Centre, Singapore (https://www.nscc.sg). 2021-12-03T05:44:59Z 2021-12-03T05:44:59Z 2021 Journal Article Chng, C., Sadovsky, Y., Hsia, K. J. & Huang, C. (2021). Site-specific peroxidation modulates lipid bilayer mechanics. Extreme Mechanics Letters, 42, 101148-. https://dx.doi.org/10.1016/j.eml.2020.101148 2352-4316 https://hdl.handle.net/10356/153450 10.1016/j.eml.2020.101148 42 101148 en R01HD086325 M4082428.050 M4082352.050 M4012229.050 Extreme Mechanics Letters 10.21979/N9/MQRTTP © 2020 Elsevier Ltd. All rights reserved. This paper was published in Extreme Mechanics Letters and is made available with permission of Elsevier Ltd. application/pdf application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Physics::Descriptive and experimental mechanics
Science::Biological sciences::Biophysics
Lipid Peroxidation
Molecular Simulation
spellingShingle Science::Physics::Descriptive and experimental mechanics
Science::Biological sciences::Biophysics
Lipid Peroxidation
Molecular Simulation
Chng, Choon-Peng
Sadovsky, Yoel
Hsia, K. Jimmy
Huang, Changjin
Site-specific peroxidation modulates lipid bilayer mechanics
description 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.
author2 School of Mechanical and Aerospace Engineering
author_facet School of Mechanical and Aerospace Engineering
Chng, Choon-Peng
Sadovsky, Yoel
Hsia, K. Jimmy
Huang, Changjin
format Article
author Chng, Choon-Peng
Sadovsky, Yoel
Hsia, K. Jimmy
Huang, Changjin
author_sort Chng, Choon-Peng
title Site-specific peroxidation modulates lipid bilayer mechanics
title_short Site-specific peroxidation modulates lipid bilayer mechanics
title_full Site-specific peroxidation modulates lipid bilayer mechanics
title_fullStr Site-specific peroxidation modulates lipid bilayer mechanics
title_full_unstemmed Site-specific peroxidation modulates lipid bilayer mechanics
title_sort site-specific peroxidation modulates lipid bilayer mechanics
publishDate 2021
url https://hdl.handle.net/10356/153450
_version_ 1759855100863447040