Marracino Paolo, Bernardi Mario, Liberti Micaela, Del Signore Federico, Trapani Erika, Gárate José-Antonio, Burnham Christian J, Apollonio Francesca, English Niall J
Department of Information Engineering, Electronics and Telecommunications, La Sapienza University, 00184 Rome, Italy.
Centro Interdisciplinario de neurociencia de Valparaiso, Universidad de Valparaiso, 05101 Valparaiso, Chile.
ACS Omega. 2018 Nov 30;3(11):15361-15369. doi: 10.1021/acsomega.8b02230. Epub 2018 Nov 13.
Electroporation characterization is a topic of intensive interest probed by extensive ongoing research efforts. Usually, these studies are carried out on lipid-bilayer electroporation. Surprisingly, the possibility of water-channel electropore formation across transmembrane proteins themselves, particularly in view of such a promising application, has not yet been elucidated. The present work examines the geometrical and kinetic aspects of electropores and their stability in such a protein milieux (as opposed through the phospholipid membranes) in depth, by means of scrutiny of such a process in human-AQP4 as a well-representative prototype. The residues forming the electropore's walls, organized in loops, reveal the formation mechanism by their dipole alignment and translational response in response to applied axial electric fields in nonequilibrium molecular dynamics simulation. The magnitude of sustaining electric fields (keeping a stable electropore open) were determined. This suggests that transmembrane proteins could play a central role in electroporation applications, e.g., in medicine and biotechnology.
电穿孔表征是一个受到广泛持续研究关注的热门话题。通常，这些研究是针对脂质双分子层电穿孔进行的。令人惊讶的是，跨膜蛋白自身形成水通道电孔的可能性，尤其是考虑到其如此有前景的应用，尚未得到阐明。本研究通过深入研究人源水通道蛋白4（AQP4）这一具有代表性的典型例子，深度考察了电孔在这种蛋白质环境（与通过磷脂膜的情况相对）中的几何结构和动力学方面及其稳定性。在非平衡分子动力学模拟中，形成电孔壁的残基以环的形式排列，通过它们在施加轴向电场时的偶极排列和平移响应揭示了形成机制。确定了维持电孔开放的稳定电场强度。这表明跨膜蛋白可能在电穿孔应用中发挥核心作用，例如在医学和生物技术领域。
