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DOI	10.1073/pnas.2004807117
	How cholesterol stiffens unsaturated lipid membranes
	Chakraborty S.; Doktorova M.; Molugu T.R.; Heberle F.A.; Scott H.L.; Dzikovski B.; Nagao M.; Stingaciu L.-R.; Standaert R.F.; Barrera F.N.; Katsaras J.; Khelashvili G.; Brown M.F.; Ashkar R.
发表日期	2020
ISSN	0027-8424
起始页码	21896
结束页码	21905
卷号	117 期号:36
英文摘要	Cholesterol is an integral component of eukaryotic cell membranes and a key molecule in controlling membrane fluidity, organization, and other physicochemical parameters. It also plays a regulatory function in antibiotic drug resistance and the immune response of cells against viruses, by stabilizing the membrane against structural damage. While it iswell understood that, structurally, cholesterol exhibits a densification effect on fluid lipid membranes, its effects on membrane bending rigidity are assumed to be nonuniversal; i.e., cholesterol stiffens saturated lipid membranes, but has no stiffening effect on membranes populated by unsaturated lipids, such as 1,2-dioleoyl-snglycero-3-phosphocholine (DOPC). This observation presents a clear challenge to structure-property relationships and to our understanding of cholesterol-mediated biological functions. Here, using a comprehensive approach - combining neutron spin-echo (NSE) spectroscopy, solid-state deuterium NMR (2H NMR) spectroscopy, and molecular dynamics (MD) simulations - we report that cholesterol locally increases the bending rigidity of DOPC membranes, similar to saturated membranes, by increasing the bilayer's packing density. All three techniques, inherently sensitive to mesoscale bending fluctuations, show up to a threefold increase in effective bending rigidity with increasing cholesterol content approaching a mole fraction of 50%. Our observations are in good agreement with the known effects of cholesterol on the area-compressibilitymodulus andmembrane structure, reaffirming membrane structure-property relationships. The current findings point to a scale-dependent manifestation of membrane properties, highlighting the need to reassess cholesterol's role in controlling membrane bending rigidity over mesoscopic length and time scales of important biological functions, such as viral budding and lipid-protein interactions. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Area compressibility; Deuterium NMR; Membrane viscosity; Molecular dynamics simulations; Neutron spin echo
语种	英语
scopus关键词	dioleoylphosphatidylcholine; unsaturated fatty acid; cholesterol; membrane lipid; Article; biological functions; cholesterol metabolism; deuteron nuclear magnetic resonance; electron spin resonance; fat content; lipid membrane; membrane structure; molecular dynamics; priority journal; protein lipid interaction; rigidity; biomechanics; cell membrane; chemistry; membrane fluidity; metabolism; nuclear magnetic resonance spectroscopy; Biomechanical Phenomena; Cell Membrane; Cholesterol; Magnetic Resonance Spectroscopy; Membrane Fluidity; Membrane Lipids; Molecular Dynamics Simulation
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160230
作者单位	Chakraborty, S., Department of Physics, Virginia Tech, Blacksburg, VA 24061, United States, Center for Soft Matter and Biological Physics, Virginia Tech, Blacksburg, VA 24061, United States; Doktorova, M., Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, TX 77030, United States; Molugu, T.R., Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States; Heberle, F.A., Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, United States, Bredesen Center, University of Tennessee, Knoxville, TN 37996, United States; Scott, H.L., Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, United States, Center for Environmental Biotechnology, University of Tennessee, Knoxville, TN 37920, United States; Dzikovski, B., ACERT, National Biomedical Center for Advanced ESR Technology, Department of Chemistry and Chemical Biology, Cornell Univer...
推荐引用方式 GB/T 7714	Chakraborty S.,Doktorova M.,Molugu T.R.,et al. How cholesterol stiffens unsaturated lipid membranes[J],2020,117(36).
APA	Chakraborty S..,Doktorova M..,Molugu T.R..,Heberle F.A..,Scott H.L..,...&Ashkar R..(2020).How cholesterol stiffens unsaturated lipid membranes.Proceedings of the National Academy of Sciences of the United States of America,117(36).
MLA	Chakraborty S.,et al."How cholesterol stiffens unsaturated lipid membranes".Proceedings of the National Academy of Sciences of the United States of America 117.36(2020).