Department of Quantitative Cell Biology, Institute of Molecular Cell Biology, University of Münster, Münster D-48149, Germany; email:
Annu Rev Biophys. 2021 May 6;50:595-616. doi: 10.1146/annurev-biophys-101920-064756. Epub 2021 Mar 12.
The ability of cells to generate mechanical forces, but also to sense, adapt to, and respond to mechanical signals, is crucial for many developmental, postnatal homeostatic, and pathophysiological processes. However, the molecular mechanisms underlying cellular mechanotransduction have remained elusive for many decades, as techniques to visualize and quantify molecular forces across individual proteins in cells were missing. The development of genetically encoded molecular tension sensors now allows the quantification of piconewton-scale forces that act upon distinct molecules in living cells and even whole organisms. In this review, we discuss the physical principles, advantages, and limitations of this increasingly popular method. By highlighting current examples from the literature, we demonstrate how molecular tension sensors can be utilized to obtain access to previously unappreciated biophysical parameters that define the propagation of mechanical forces on molecular scales. We discuss how the methodology can be further developed and provide a perspective on how the technique could be applied to uncover entirely novel aspects of mechanobiology in the future.
细胞产生机械力的能力，以及感知、适应和响应机械信号的能力，对于许多发育、出生后稳态和病理生理过程至关重要。然而，几十年来，由于缺乏可视化和量化细胞中单一蛋白质上分子力的技术，细胞力学转导的分子机制仍然难以捉摸。遗传编码分子张力传感器的发展现在允许量化作用于活细胞甚至整个生物体中不同分子的皮牛顿级力。在这篇综述中，我们讨论了这种越来越流行的方法的物理原理、优点和局限性。通过突出文献中的当前示例，我们展示了如何利用分子张力传感器来获得以前未被重视的定义分子尺度上机械力传播的生物物理参数。我们讨论了如何进一步开发该方法，并就该技术如何应用于未来揭示机械生物学全新方面提供了一个视角。
