Discoveries in structure and physiology of mechanically activated ion channels

Nature, Journal Year: 2020, Volume and Issue: 587(7835), P. 567 - 576

Published: Nov. 25, 2020

Language: Английский

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Stimuli‐Responsive Nanocomposite Hydrogels for Biomedical Applications

Advanced Functional Materials, Journal Year: 2020, Volume and Issue: 31(8)

Published: Nov. 18, 2020

Abstract The complex tissue‐specific physiology that is orchestrated from the nano‐ to macroscale, in conjugation with dynamic biophysical/biochemical stimuli underlying biological processes, has inspired design of sophisticated hydrogels and nanoparticle systems exhibiting stimuli‐responsive features. Recently, nanoparticles have been combined advanced nanocomposite hybrid platforms expanding their range biomedical applications. ease flexibility attaining modular hydrogel constructs by selecting different classes nanomaterials/hydrogels, or tuning nanoparticle‐hydrogel physicochemical interactions widely expands attainable properties levels beyond those traditional platforms. This review showcases intrinsic ability react external internal/physiological scope developing intelligent application‐oriented Moreover, are overviewed context encoding cascades recapitulate signaling interplays present native biosystems. Collectively, recent breakthroughs improve potential for operating as applications benefit tailored single multi‐responsiveness.

Language: Английский

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Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: May 31, 2021

Macrophages perform diverse functions within tissues during immune responses to pathogens and injury, but molecular mechanisms by which physical properties of the tissue regulate macrophage behavior are less well understood. Here, we examine role mechanically activated cation channel Piezo1 in polarization sensing microenvironmental stiffness. We show that macrophages lacking exhibit reduced inflammation enhanced wound healing responses. Additionally, expressing transgenic Ca2+ reporter, Salsa6f, reveal influx is dependent on Piezo1, modulated soluble signals, stiff substrates. Furthermore, stiffness-dependent changes function, both vitro response subcutaneous implantation biomaterials vivo, require Piezo1. Finally, positive feedback between actin drives activation. Together, our studies a mechanosensor stiffness macrophages, its activity modulates

Language: Английский

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The mechanosensitive Piezo1 channel is required for bone formation

eLife, Journal Year: 2019, Volume and Issue: 8

Published: July 10, 2019

Mechanical load of the skeleton system is essential for development, growth, and maintenance bone. However, molecular mechanism by which mechanical stimuli are converted into osteogenesis bone formation remains unclear. Here we report that Piezo1, a bona fide mechanotransducer critical various biological processes, plays role in formation. Knockout Piezo1 osteoblast lineage cells disrupts osteoblasts severely impairs structure strength. Bone loss induced unloading blunted knockout mice. Intriguingly, simulated microgravity treatment reduced function suppressing expression Piezo1. Furthermore, osteoporosis patients show closely correlated with dysfunction. These data collectively suggest functions as key conferring mechanosensitivity to determining mechanical-load-dependent formation, represents novel therapeutic target treating or unloading-induced severe loss.

Language: Английский

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Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 24, 2022

Abstract Cancer microenvironment is critical for tumorigenesis and cancer progression. The extracellular matrix (ECM) interacts with tumor stromal cells to promote proliferation, migration, invasion, angiogenesis immune evasion. Both ECM itself stiffening-induced mechanical stimuli may activate cell membrane receptors mechanosensors such as integrin, Piezo1 TRPV4, thereby modulating the malignant phenotype of cells. A better understanding how stiffness regulates progression will contribute development new therapeutics. rapidly expanding evidence in this research area suggests that regulators effectors represent potential therapeutic targets cancer. This review summarizes recent work on regulation cancer, effects progression, immunity drug resistance. We also discuss be druggable intervene Based these advances, future efforts can made develop more effective safe drugs interrupt stiffness-induced oncogenic signaling,

Language: Английский

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Piezo1/2 mediate mechanotransduction essential for bone formation through concerted activation of NFAT-YAP1-ß-catenin

eLife, Journal Year: 2020, Volume and Issue: 9

Published: March 18, 2020

Mechanical forces are fundamental regulators of cell behaviors. However, molecular regulation mechanotransduction remain poorly understood. Here, we identified the mechanosensitive channels Piezo1 and Piezo2 as key force sensors required for bone development osteoblast differentiation. Loss Piezo1, or more severely Piezo1/2, in mesenchymal progenitor cells, led to multiple spontaneous fractures newborn mice due inhibition differentiation increased resorption. In addition, loss Piezo1/2 rendered resistant further caused by unloading both homeostasis. Mechanistically, relayed fluid shear stress extracellular matrix stiffness signals activate Ca2+ influx stimulate Calcineurin, which promotes concerted activation NFATc1, YAP1 ß-catenin transcription factors inducing their dephosphorylation well NFAT/YAP1/ß-catenin complex formation. Yap1 activities were reduced mutant bones such defects partially rescued enhanced activities.

Language: Английский

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Mechanosensitive Ion Channels: Structural Features Relevant to Mechanotransduction Mechanisms

Annual Review of Neuroscience, Journal Year: 2020, Volume and Issue: 43(1), P. 207 - 229

Published: Feb. 22, 2020

Activation of mechanosensitive ion channels underlies a variety fundamental physiological processes that require sensation mechanical force. Different adapt distinctive structures and mechanotransduction mechanisms to fit their biological roles. How work, especially in animals, has been extensively studied the past decade. Here we review key findings functional structural characterizations these highlight features relevant mechanism each specific channel.

Language: Английский

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Myosin-II mediated traction forces evoke localized Piezo1-dependent Ca2+ flickers

Communications Biology, Journal Year: 2019, Volume and Issue: 2(1)

Published: Aug. 7, 2019

Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, tissue homeostasis, regeneration. Studies on Piezo1 have largely focused transduction of "outside-in" forces, its response internal, cell-generated forces remains poorly understood. Here, using measurements endogenous activity traction in native cellular conditions, we show that generate spatially-restricted Piezo1-mediated Ca

Language: Английский

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The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration

Neuron, Journal Year: 2019, Volume and Issue: 102(2), P. 373 - 389.e6

Published: Feb. 25, 2019

Language: Английский

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Mammalian Mechanoelectrical Transduction: Structure and Function of Force-Gated Ion Channels

Cell, Journal Year: 2019, Volume and Issue: 179(2), P. 340 - 354

Published: Oct. 1, 2019

Language: Английский

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