Ashrafuzzaman Mohammad, Koeppe Roger E, Andersen Olaf S
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA.
Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA.
Int J Mol Sci. 2024 Feb 27;25(5):2758. doi: 10.3390/ijms25052758.
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 H 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.
双层材料特性（厚度、脂质固有曲率和弹性模量）的扰动会调节不同膜蛋白构象之间的自由能差，从而导致跨双层蛋白的构象偏好发生变化。为了进一步探究曲率和弹性在决定作为通道功能调节基础的双层特性变化中的相对重要性，我们研究了形成胶束的两亲分子Triton X-100、还原型Triton X-100和H脂质相促进剂辣椒素如何调节短杆菌肽和短杆菌酪肽通道的功能。无论两亲分子诱导的固有曲率变化是负向还是正向，添加两亲分子都会增加短杆菌肽通道的出现率和寿命，并稳定短杆菌酪肽通道中的高电导状态。然而，当通过改变磷脂头部基团相互作用来调节固有曲率时，促进负向曲率的操作会稳定短杆菌酪肽通道中的高电导状态，但会使短杆菌肽通道不稳定。使用不同长度的短杆菌肽通道来探测双层弹性的变化，我们发现两亲分子吸附会增加双层弹性，而改变头部基团相互作用则不会。我们得出以下结论：第一，证实了先前的研究，短杆菌酪肽和短杆菌肽通道都受到脂质双层材料特性变化的调节，这些变化同时发生，但因所改变的特性不同而有所差异；第二，孤立的负向曲率变化会稳定短杆菌酪肽通道中的较高电流水平，并使短杆菌肽通道不稳定；第三，双层弹性的增加会稳定短杆菌酪肽通道中的较高电流水平，并稳定短杆菌肽通道；第四，弹性变化的能量后果往往比曲率变化更具主导性。
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