Kondrashov Oleg V, Galimzyanov Timur R, Molotkovsky Rodion J, Batishchev Oleg V, Akimov Sergey A
Laboratory of Bioelectrochemistry, A.N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, 31/4 Leninskiy Prospekt, 119071 Moscow, Russia.
Membranes (Basel). 2020 Nov 25;10(12):368. doi: 10.3390/membranes10120368.
The lipid matrix of cellular membranes is an elastic liquid crystalline medium. Its deformations regulate the functionality and interactions of membrane proteins,f membrane-bound peptides, lipid and protein-lipid domains. Gramicidin A (gA) is a peptide, which incorporates into membrane leaflets as a monomer and may form a transmembrane dimer. In both configurations, gA deforms the membrane. The transmembrane dimer of gA is a cation-selective ion channel. Its electrical response strongly depends on the elastic properties of the membrane. The gA monomer and dimer deform the membrane differently; therefore, the elastic energy contributes to the activation barriers of the dimerization and dissociation of the conducting state. It is shown experimentally that channel characteristics alter if gA molecules have been located in the vicinity of the conducting dimer. Here, based on the theory of elasticity of lipid membranes, we developed a quantitative theoretical model which allows explaining experimentally observed phenomena under conditions of high surface density of gA or its analogues, i.e., in the regime of strong lateral interactions of gA molecules, mediated by elastic deformations of the membrane. The model would be useful for the analysis and prediction of the gA electrical response in various experimental conditions. This potentially widens the possible applications of gA as a convenient molecular sensor of membrane elasticity.
细胞膜的脂质基质是一种弹性液晶介质。其变形调节膜蛋白、膜结合肽、脂质和脂蛋白结构域的功能及相互作用。短杆菌肽A（gA）是一种肽，它以单体形式掺入膜小叶中，并可能形成跨膜二聚体。在这两种构型中，gA都会使膜变形。gA的跨膜二聚体是一种阳离子选择性离子通道。其电响应强烈依赖于膜的弹性特性。gA单体和二聚体对膜的变形方式不同；因此，弹性能有助于传导状态二聚化和解离的活化能垒。实验表明，如果gA分子位于传导二聚体附近，通道特性会发生改变。在此，基于脂质膜弹性理论，我们开发了一个定量理论模型，该模型能够解释在gA或其类似物高表面密度条件下，即gA分子通过膜的弹性变形介导的强横向相互作用机制下，实验观察到的现象。该模型将有助于分析和预测gA在各种实验条件下的电响应。这可能会拓宽gA作为一种方便的膜弹性分子传感器的潜在应用范围。
