The immune system performs critical functions to defend against invading pathogens and maintain tissue homeostasis. Immune cells reside within or are recruited to a host of mechanically active tissues throughout the body and, as a result, are exposed to varying types and degrees of mechanical stimuli. Despite their abundance in such tissues, the role of mechanical stimuli in influencing immune cell function and the molecular mechanisms responsible for mechanics-mediated changes are still poorly understood. The recent emergence of mechanically-gated ion channels, particularly Piezo1, has provided an exciting avenue of research within the fields of mechanobiology and immunology. Numerous studies have identified roles for mechanically-gated ion channels in mechanotransduction within various different cell types, with a few recent studies in immune cells. These initial studies provide strong evidence that mechanically-gated ion channels play pivotal roles in regulating the immune system. In this review, we discuss characteristics of ion channel mediated force transduction, review the current techniques used to quantify and visualize ion channel activity in response to mechanical stimuli, and finally we provide an overview of recent studies examining the role of mechanically-gated ion channels in modulating immune cell function.
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http://dx.doi.org/10.1016/j.cossms.2021.100951 | DOI Listing |
Neuron
December 2024
Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, China; Department of Neurobiology, School of Basic Medicine, Capital Medical University, Beijing, China; Institute for Medical Physiology, Chinese Institutes for Medical Research, Beijing, China. Electronic address:
Mammalian transmembrane channel-like proteins 1 and 2 (TMC1 and TMC2) have emerged as very promising candidate mechanotransduction channels in hair cells. However, controversy persists because the heterogeneously expressed TMC1/2 in cultured cells lack evidence of mechanical gating, primarily due to their absence from the plasma membrane. By employing domain swapping with OSCA1.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Laboratory of Cell Biology, Department of Orthopedic Surgery, University Hospital of Tübingen, Waldhörnlestraße 22, D-7207, Tübingen, Germany.
Mechanosensation allows cells to generate intracellular signals in response to mechanical cues from their environment. Previous research has demonstrated that mechanical stress can alter the mechanical properties of the nucleus, affecting gene transcription, chromatin methylation, and nuclear mechanoprotection during mechanical loading. PIEZO1, a mechanically gated Ca ion channel, has been shown to be important in sensing mechanical stress, however its signal transduction pathway is not thoroughly understood.
View Article and Find Full Text PDFPNAS Nexus
November 2024
Department of Biomedical Engineering, University of California, Irvine, Irvine 92697, USA.
Macrophages in the vascular wall ingest and clear lipids, but abundant lipid accumulation leads to foam cell formation and atherosclerosis, a pathological condition often characterized by tissue stiffening. While the role of biochemical stimuli in the modulation of macrophage function is well studied, the role of biophysical cues and the molecules involved in mechanosensation are less well understood. Here, we use genetic and pharmacological tools to show extracellular oxidized low-density lipoproteins (oxLDLs) stimulate Ca signaling through activation of the mechanically gated ion channel Piezo1.
View Article and Find Full Text PDFJ Gen Physiol
December 2024
Enteric NeuroScience Program (ENSP), Mayo Clinic, Rochester, MN, USA.
Piezo2 is a mechanically gated ion channel most commonly expressed by specialized mechanoreceptors, such as the enteroendocrine cells (EECs) of the gastrointestinal epithelium. A subpopulation of EECs expresses Piezo2 and functionally resembles the skin's touch sensors, called Merkel cells. Low-magnitude mechanical stimuli delivered to the mucosal layer are primarily sensed by mechanosensitive EECs in a process we term "gut touch.
View Article and Find Full Text PDFBrain
October 2024
Molecular Physiology of Somatic Sensation Laboratory, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 10409, Germany.
PIEZO2 is a trimeric mechanically-gated ion channel expressed by most sensory neurons in the dorsal root ganglia. Mechanosensitive PIEZO2 channels are also genetically required for normal touch sensation in both mice and humans. We previously showed that PIEZO2 channels are also strongly modulated by membrane voltage.
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