Ion Channels in Biophysics and Physiology: Methods & Challenges to Study Mechanosensitive Ion Channels.
Ion Channels in Biophysics and Physiology: Methods & Challenges to Study Mechanosensitive Ion Channels.
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DOI：
10.1007/978-981-16-4254-8_3
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发表时间：
2021
影响因子：
--
通讯作者：
Y. Luo;Jérôme J. Lacroix
中科院分区：
文献类型：
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作者：
Y. Luo;Jérôme J. Lacroix
B爵士在1950年发表的一部开创性著作中。Katz表明，青蛙肌梭的电反应直接随肌肉拉伸的速率和幅度而变化。这一观察使他提出了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）。尽管有这些早期的工作，负责将机械刺激转化为生物信号的分子的身份几十年来一直被隐藏着。这种延迟通常归因于精确量化生物样品的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相比，定量细胞膜的机械变形并不简单。机械力产生一系列复杂的膜变形，包括弯曲、变薄、压缩、膨胀和剪切，因此具有许多应变维度的分量。此外，由于细胞的粘弹性性质，这些变形可能具有线性和非线性分量。尽管存在这些实验挑战，Sukharev等人从细菌中克隆了第一个机械敏感离子通道。在20世纪90年代中期发现了大肠杆菌（Sukharev等，Nature，265-268，1994）。20年后，包含数十个真核机械敏感离子通道的几个蛋白质家族已经被鉴定出来，描绘了力激活分子机器的惊人多样性。在这一章中，我们打算提供一个概述的知识和技术挑战的现状，研究细胞膜如何变形后的机械应力和离子通道蛋白如何检测这些变形从事稳态细胞反应。
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 bacteriaE. coliin 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.