College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.
College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA.
Adv Exp Med Biol. 2021;1349:33-49. doi: 10.1007/978-981-16-4254-8_3.
In a seminal work published in 1950, Sir B. Katz showed that the electrical response of the frog muscle spindle varies directly with the rate and amplitude of muscle stretch. This observation led him to propose the existence of a piezoelectric substance in this organ, setting the stage for the field of mechanobiology (Katz, J Physiol 111, 261-282, 1950). Despite this early work, the identity of the molecules responsible for the conversion of mechanical stimuli into biological signals has remained hidden for decades. This delay is often attributed to the inherent difficulty to precisely quantify the mechanical deformations of biological samples. In contrast to other forms of stimuli such as ligand concentration and membrane potential, quantifying mechanical deformations of cell membranes is not trivial. Mechanical forces produce a complex array of membrane deformations including bending, thinning, compression, expansion, and shear, and thus, have components in many strain dimensions. In addition, due to the viscoelastic nature of cells, these deformations may have linear and nonlinear components. In spite of these experimental challenges, Sukharev et al. cloned the first mechanosensitive ion channel from the bacteria E. coli in the mid-1990s (Sukharev et al. Nature, 265-268, 1994). Two decades later, several protein families encompassing dozens of eukaryotic mechanosensitive ion channels have been identified, depicting an astonishing diversity of force-activated molecular machines. In this chapter, we intend to provide an overview of the current state of knowledge and technical challenges to study how cell membranes deform upon mechanical stress and how ion channel proteins detect these deformations to engage homeostatic cellular responses.
在 1950 年发表的一篇开创性论文中，B. Katz 爵士表明，青蛙肌梭的电反应与肌肉拉伸的速度和幅度直接相关。这一观察结果使他提出在这个器官中存在压电物质，为机械生物学领域奠定了基础（Katz，J Physiol 111, 261-282, 1950）。尽管有这项早期工作，但负责将机械刺激转化为生物信号的分子的身份在几十年中仍然隐藏着。这种延迟通常归因于精确量化生物样本机械变形的固有困难。与其他形式的刺激（如配体浓度和膜电位）不同，量化细胞膜的机械变形并不简单。机械力会产生一系列复杂的膜变形，包括弯曲、变薄、压缩、膨胀和剪切，因此，在许多应变维度上都有成分。此外，由于细胞的粘弹性，这些变形可能具有线性和非线性成分。尽管存在这些实验挑战，但 Sukharev 等人在 20 世纪 90 年代中期从细菌大肠杆菌中克隆出了第一个机械敏感离子通道（Sukharev 等人，自然，265-268, 1994）。二十年后，已经鉴定出了包含数十种真核机械敏感离子通道的几个蛋白家族，描绘了令人惊讶的力激活分子机器多样性。在本章中，我们旨在提供对当前知识状态和技术挑战的概述，以研究细胞膜在机械应力下如何变形，以及离子通道蛋白如何检测这些变形以引发稳态细胞反应。
