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Intrinsic Lipid Curvature and Bilayer Elasticity as Regulators of Channel Function: A Comparative Single-Molecule Study.
Ashrafuzzaman, Mohammad; Koeppe, Roger E; Andersen, Olaf S.
Affiliation
  • Ashrafuzzaman M; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA.
  • Koeppe RE; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA.
  • Andersen OS; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA.
Int J Mol Sci ; 25(5)2024 Feb 27.
Article in En | MEDLINE | ID: mdl-38474005
ABSTRACT
Perturbations in bilayer material properties (thickness, lipid intrinsic curvature and elastic moduli) modulate the free energy difference between different membrane protein conformations, thereby leading to changes in the conformational preferences of bilayer-spanning proteins. To further explore the relative importance of curvature and elasticity in determining the changes in bilayer properties that underlie the modulation of channel function, we investigated how the micelle-forming amphiphiles Triton X-100, reduced Triton X-100 and the HII lipid phase promoter capsaicin modulate the function of alamethicin and gramicidin channels. Whether the amphiphile-induced changes in intrinsic curvature were negative or positive, amphiphile addition increased gramicidin channel appearance rates and lifetimes and stabilized the higher conductance states in alamethicin channels. When the intrinsic curvature was modulated by altering phospholipid head group interactions, however, maneuvers that promote a negative-going curvature stabilized the higher conductance states in alamethicin channels but destabilized gramicidin channels. Using gramicidin channels of different lengths to probe for changes in bilayer elasticity, we found that amphiphile adsorption increases bilayer elasticity, whereas altering head group interactions does not. We draw the following

conclusions:

first, confirming previous studies, both alamethicin and gramicidin channels are modulated by changes in lipid bilayer material properties, the changes occurring in parallel yet differing dependent on the property that is being changed; second, isolated, negative-going changes in curvature stabilize the higher current levels in alamethicin channels and destabilize gramicidin channels; third, increases in bilayer elasticity stabilize the higher current levels in alamethicin channels and stabilize gramicidin channels; and fourth, the energetic consequences of changes in elasticity tend to dominate over changes in curvature.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gramicidin / Lipid Bilayers Language: En Journal: Int J Mol Sci Year: 2024 Type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gramicidin / Lipid Bilayers Language: En Journal: Int J Mol Sci Year: 2024 Type: Article Affiliation country: United States