Webster Samantha, Brynn Remi, Poole Kate
School of Biomedical Sciences, Faculty of Medicine & Health, University of New South Wales, Sydney, NSW 2052, Australia.
J Cell Sci. 2025 Aug 1;138(15). doi: 10.1242/jcs.264038.
Mechanosensitive ion channels are found across all classes of life, suggesting that cellular force sensing is an ancient sense. In mammals, mechanosensitive ion channels are expressed in many cells and tissues, and disrupting their function can impact an array of physiological processes. The identification and characterisation of mammalian mechanosensitive ion channels has been driven by in vitro patch-clamp electrophysiology studies. However, challenges arise when applying insights from these biophysical measurements across scales. Electrophysiology studies do not capture the complexity of force sensing in vivo, where the nature of mechanical loading, the mechanics of the local environment and the co-expression of accessory molecules can all influence mechanosensitive ion channel function. In addition, a nuanced perspective acknowledging the varying roles that ion channels can play in force-sensing pathways and the distinctions in activation profiles of mechanosensitive ion channels is required to better understand channel-mediated mechanotransduction. In this Opinion article, by synthesising our knowledge of these activation profiles gleaned from in vitro studies, we argue that only by considering mechanosensitive ion channel function within an appropriate cellular and mechanical context will we be able to better understand the roles of this fascinating class of molecule in mammalian cells in vivo.
机械敏感离子通道存在于所有生命类别中，这表明细胞力感知是一种古老的感觉。在哺乳动物中，机械敏感离子通道在许多细胞和组织中表达，破坏它们的功能会影响一系列生理过程。哺乳动物机械敏感离子通道的鉴定和表征一直受到体外膜片钳电生理学研究的推动。然而，当将这些生物物理测量的见解应用于不同尺度时，会出现挑战。电生理学研究无法捕捉体内力感知的复杂性，在体内，机械负荷的性质、局部环境的力学以及辅助分子的共表达都会影响机械敏感离子通道的功能。此外，需要一种细致入微的观点，承认离子通道在力感知途径中可以发挥的不同作用以及机械敏感离子通道激活模式的差异，以便更好地理解通道介导的机械转导。在这篇观点文章中，通过综合我们从体外研究中获得的关于这些激活模式的知识，我们认为只有在适当的细胞和力学背景下考虑机械敏感离子通道的功能，我们才能更好地理解这类迷人的分子在体内哺乳动物细胞中的作用。
