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Mechanosensitive ion channels are a class of membrane-integrated proteins that convert externalmechanical forces, including stretching, pressure, gravity, and osmotic pressure changes, some of which can be caused by pathogen invasion, into electrical and chemical signals transmitted to the cytoplasm. In recent years, with the identification of many of these channels, their roles in the initiation and progression of many diseases have been gradually revealed. Multiple studies have shown that mechanosensitive ion channels regulate the proliferation, activation, and inflammatory responses of immune cells by being expressed on the surface of immune cells and further responding to mechanical forces. Nonetheless, further clarification is required regarding the signaling pathways of immune-cell pattern-recognition receptors and on the impact of microenvironmental changes and mechanical forces on immune cells. This review summarizes the roles of mechanosensitive ion channels in immune cells.

Membrane forces shift the equilibria of mechanosensitive channels enabling them to convert mechanical cues into electrical signals. Molecular tools to stabilize and methods to capture their highly dynamic states are lacking. Cyclodextrins can mimic tension through the sequestering of lipids from membranes. Here we probe the conformational ensemble of MscS by EPR spectroscopy, the lipid environment with NMR, and function with electrophysiology under cyclodextrin-induced tension. We show the extent of MscS activation depends on the cyclodextrin-to-lipid ratio, and that lipids are depleted slower when MscS is present. This has implications in MscS' activation kinetics when distinct membrane scaffolds such as nanodiscs or liposomes are used. We find MscS transits from closed to sub-conducting state(s) before it desensitizes, due to the lack of lipid availability in its vicinity required for closure. Our approach allows for monitoring tension-sensitive states in membrane proteins and screening molecules capable of inducing molecular tension in bilayers. [Display omitted] • Our approach allows the monitoring of tension-sensitive states in membrane proteins • MscS conformational ensemble was probed by EPR spectroscopy under molecular tension • The lipid environment within nanodiscs was monitored using NMR spectroscopy • Electrophysiology measurements with cyclodextrin revealed MscS functional states Lane, Ma, Yan et al. demonstrate that the conformational ensemble of the mechanosensitive channel MscS can be monitored by EPR spectroscopy, the associated lipid environment by NMR, and single-channel transitions can be followed by electrophysiology under cyclodextrin-induced membrane tension. [ABSTRACT FROM AUTHOR]

Objective: To summarize the role of Piezo mechanosensitive ion channels in the osteoarticular system, in order to provide reference for subsequent research., Methods: Extensive literature review was conducted to summarize the structural characteristics, gating mechanisms, activators and blockers of Piezo ion channels, as well as their roles in the osteoarticular systems., Results: The osteoarticular system is the main load-bearing and motor tissue of the body, and its ability to perceive and respond to mechanical stimuli is one of the guarantees for maintaining normal physiological functions of bones and joints. The occurrence and development of many osteoarticular diseases are closely related to abnormal mechanical loads. At present, research shows that Piezo mechanosensitive ion channels differentiate towards osteogenesis by responding to stretching stimuli and regulating cellular Ca 2+ influx signals; and it affects the proliferation and migration of osteoblasts, maintaining bone homeostasis through cellular communication between osteoblasts-osteoclasts. Meanwhile, Piezo1 protein can indirectly participate in regulating the formation and activity of osteoclasts through its host cells, thereby regulating the process of bone remodeling. During mechanical stimulation, the Piezo1 ion channel maintains bone homeostasis by regulating the expressions of Akt and Wnt1 signaling pathways. The sensitivity of Piezo1/2 ion channels to high strain mechanical signals, as well as the increased sensitivity of Piezo1 ion channels to mechanical transduction mediated by Ca 2+ influx and inflammatory signals in chondrocytes, is expected to become a new entry point for targeted prevention and treatment of osteoarthritis. But the specific way mechanical stimuli regulate the physiological/pathological processes of bones and joints still needs to be clarified., Conclusion: Piezo mechanosensitive ion channels give the osteoarticular system with important abilities to perceive and respond to mechanical stress, playing a crucial mechanical sensing role in its cellular fate, bone development, and maintenance of bone and cartilage homeostasis.