Beedle Amy Em, Garcia-Manyes Sergi
Department of Physics, Randall Centre for Cell and Molecular Biophysics, Centre for the Physical Science of Life and London Centre for Nanotechnology, King's College London, Strand, WC2R 2LS London, United Kingdom.
Institute for Bioengineering of Catalonia (IBEC), the Barcelona Institute of Technology (BIST), 08028 Barcelona, Spain.
Nat Rev Mater. 2023 Jan;8:10-24. doi: 10.1038/s41578-022-00488-z. Epub 2022 Oct 24.
In addition to biochemical signals and genetic considerations, mechanical forces are rapidly emerging as a master regulator of human physiology. Yet the molecular mechanisms that regulate force-induced functionalities across a wide range of scales, encompassing the cell, tissue or organ levels, are comparatively not so well understood. With the advent, development and refining of single molecule nanomechanical techniques, enabling to exquisitely probe the conformational dynamics of individual proteins under the effect of a calibrated force, we have begun to acquire a comprehensive knowledge on the rich plethora of physicochemical principles that regulate the elasticity of single proteins. Here we review the major advances underpinning our current understanding of how the elasticity of single proteins regulates mechanosensing and mechanotransduction. We discuss the present limitations and future challenges of such a prolific and burgeoning field.
除了生化信号和遗传因素外,机械力正迅速成为人类生理学的主要调节因子。然而,在从细胞、组织到器官水平的广泛尺度上调节力诱导功能的分子机制,相对而言还不太为人所理解。随着单分子纳米力学技术的出现、发展和完善,能够精确探测单个蛋白质在校准力作用下的构象动力学,我们已经开始全面了解调节单个蛋白质弹性的丰富物理化学原理。在这里,我们回顾了支撑我们目前对单个蛋白质弹性如何调节机械传感和机械转导理解的主要进展。我们讨论了这个多产且蓬勃发展的领域目前的局限性和未来的挑战。