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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 is well 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-sn-glycero-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-compressibility modulus and membrane 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.
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Bending rigidity of charged lipid bilayer membranes
We experimentally investigate the effect of lipid charge on the stiffness of bilayer membranes. The bending rigidity of membranes with composition 0–100 mol% of charged lipids, in the absence and presence of salt at different concentrations, is measured with the flicker spectroscopy method, using the shape fluctuations of giant unilamellar vesicles. The analysis considers both the mean squared amplitudes and the time autocorrelations of the shape modes. Our results show that membrane charge increases the bending rigidity relative to the charge-free membrane. The effect is diminished by the addition of monovalent salt to the suspending solutions. The trend shown by the membrane bending rigidity correlates with zeta potential measurements, confirming charge screening at different salt concentrations. The experimental results in the presence of salt are in good agreement with existing theories of membrane stiffening by surface charge.
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- PAR ID:
- 10105357
- Date Published:
- Journal Name:
- Soft Matter
- ISSN:
- 1744-683X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/C9SM00772E
