Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 31, 2023

Abstract Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical regarding cell activities and metabolism. Typical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, viscosity. Mechanotransduction has been expected trigger multiple such as embryonic development, repair regeneration. However, prolonged excessive stimulation can result pathological multi-organ fibrosis, tumorigenesis, cancer immunotherapy resistance. Although associations between normal homeostasis diseases have identified, regulatory mechanisms among different are not yet comprehensively illustrated, no effective therapies currently available targeting cue-related signaling. This review systematically summarizes characteristics typical conditions with updated evidence. The key effectors responding stimulations listed, Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator PDZ-binding motif (TAZ), transient receptor potential vanilloid 4 (TRPV4). We also reviewed signaling pathways, therapeutic targets cutting-edge clinical applications related cues.

Language: Английский

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Ultrasound-Responsive Systems as Components for Smart Materials

Chemical Reviews, Journal Year: 2021, Volume and Issue: 122(5), P. 5165 - 5208

Published: Nov. 12, 2021

Smart materials can respond to stimuli and adapt their responses based on external cues from environments. Such behavior requires a way transport energy efficiently then convert it for use in applications such as actuation, sensing, or signaling. Ultrasound carry safely with low losses through complex opaque media. It be localized small regions of space couple systems over wide range time scales. However, the same characteristics that allow ultrasound propagate make difficult acoustic into other useful forms. Recent work across diverse fields has begun address this challenge, demonstrating ultrasonic effects provide control physical chemical surprisingly high specificity. Here, we review recent progress ultrasound-matter interactions, focusing incorporated components smart materials. These techniques build fundamental phenomena cavitation, microstreaming, scattering, radiation forces enable capabilities payload delivery, initiation biological processes. The diversity emerging holds great promise supported by poses interesting questions further investigations.

Language: Английский

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Structure, kinetic properties and biological function of mechanosensitive Piezo channels

Cell & Bioscience, Journal Year: 2021, Volume and Issue: 11(1)

Published: Jan. 9, 2021

Abstract Mechanotransduction couples mechanical stimulation with ion flux, which is critical for normal biological processes involved in neuronal cell development, pain sensation, and red blood volume regulation. Although they are key mechanotransducers, mechanosensitive channels mammals have remained difficult to identify. In 2010, Coste colleagues revealed a novel family of mechanically activated cation eukaryotes, consisting Piezo1 Piezo2 channels. These been proposed as the long-sought-after mammals. exhibit unique propeller-shaped architecture implicated mechanotransduction various processes, including touch balance, cardiovascular Furthermore, several mutations Piezo shown cause multiple hereditary human disorders, such autosomal recessive congenital lymphatic dysplasia. Notably, that dehydrated xerocytosis alter rate channel inactivation, indicating role their kinetics physiology. Given importance understanding process, this review focuses on structural details, kinetic properties potential function mechanosensors. We also briefly diseases caused by genes, these proteins.

Language: Английский

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Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 26, 2022

Mechanical damage is one of the predisposing factors inflammation, and it runs through entire inflammatory pathological process. Repeated or persistent damaging mechanical irritation leads to chronic diseases. The mechanism how forces induce inflammation not fully understood. Piezo1 a newly discovered mechanically sensitive ion channel. channel opens in response stimuli, transducing signals into an cascade cell leading tissue inflammation. A large amount evidence shows that plays vital role occurrence progression This mini-review briefly presents new responds different stresses trigger various tissues. discovery provides insights for treatment diseases related stress. Inhibiting transduction can inhibit improve outcome at early stage. pharmacology has shown bright prospects. development tissue-specific drugs clinical use may be target treating

Language: Английский

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Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 9, 2022

Ultrasound has been used to non-invasively manipulate neuronal functions in humans and other animals. However, this approach is limited as it challenging target specific cells within the brain or body. Here, we identify human Transient Receptor Potential A1 (hsTRPA1) a candidate that confers ultrasound sensitivity mammalian cells. Ultrasound-evoked gating of hsTRPA1 specifically requires its N-terminal tip region cholesterol interactions; with an intact actin cytoskeleton, revealing elements sonogenetic mechanism. Next, use calcium imaging electrophysiology show potentiates ultrasound-evoked responses primary neurons. Furthermore, unilateral expression mouse layer V motor cortical neurons leads c-fos contralateral limb response delivered through skull. Collectively, demonstrate hsTRPA1-based sonogenetics can effectively brain, method could be across species.

Language: Английский

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Microglial amyloid beta clearance is driven by PIEZO1 channels

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: June 15, 2022

Microglia are the endogenous immune cells of brain and act as sensors pathology to maintain homeostasis eliminate potential threats. In Alzheimer's disease (AD), toxic amyloid beta (Aβ) accumulates in forms stiff plaques. late-onset AD accounting for 95% all cases, this is thought be due reduced clearance Aβ. Human genome-wide association studies animal models suggest that results from aberrant function microglia. While impact neurochemical pathways on microglia had been broadly studied, mechanical receptors regulating microglial functions remain largely unexplored.Here we showed a mechanotransduction ion channel, PIEZO1, expressed functional human mouse We used small molecule agonist, Yoda1, study how activation PIEZO1 affects AD-related induced pluripotent stem cell (iPSC)-derived microglia-like (iMGL) under controlled laboratory experiments. Cell survival, metabolism, phagocytosis lysosomal activity were assessed using real-time assays. To evaluate effect vivo, 5-month-old 5xFAD male mice infused daily with Yoda1 two weeks through intracranial cannulas. Microglial Iba1 expression Aβ quantified immunohistochemistry confocal microscopy. Published datasets in-depth analysis gene related subpopulations.We show orchestrates by enhancing phagocytosis, activity. inhibited PIEZO1-mediated calcium transients, whereas selective improved resulting both AD. Moreover, was associated unique transcriptional phenotype indicated assessment cellular single-cell datasets.These indicate compromised could channels alleviated burden. Pharmacological regulation these mechanoreceptors represent novel therapeutic paradigm

Language: Английский

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Induction of a torpor-like hypothermic and hypometabolic state in rodents by ultrasound

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(5), P. 789 - 803

Published: May 25, 2023

Abstract Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise safe induction of a torpor-like hypothermic hypometabolic rodents by remote transcranial ultrasound stimulation at hypothalamus preoptic area (POA). We achieve long-lasting (>24 h) mice via closed-loop feedback control with automated detection temperature. Ultrasound-induced hypothermia hypometabolism (UIH) triggered activation POA neurons, involves dorsomedial as downstream brain region subsequent inhibition thermogenic brown adipose tissue. Single-nucleus RNA-sequencing neurons reveals TRPM2 ultrasound-sensitive ion channel, knockdown suppresses UIH. also demonstrate that UIH feasible non-torpid animal, rat. Our findings establish promising technology for noninvasive state.

Language: Английский

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The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(18)

Published: April 25, 2023

Transcranial low-intensity ultrasound is a promising neuromodulation modality, with the advantages of noninvasiveness, deep penetration, and high spatiotemporal accuracy. However, underlying biological mechanism ultrasonic remains unclear, hindering development efficacious treatments. Here, well-known Piezo1 was studied through conditional knockout mouse model as major mediator for ex vivo in vivo. We showed that (P1KO) right motor cortex mice significantly reduced ultrasound-induced neuronal calcium responses, limb movement, muscle electromyogram (EMG) responses. also detected higher expression central amygdala (CEA), which found to be more sensitive stimulation than was. Knocking out CEA neurons significant reduction response under stimulation, while knocking astrocytic no-obvious changes Additionally, we excluded an auditory confound by monitoring cortical activation using smooth waveform randomized parameters stimulate P1KO ipsilateral contralateral regions same brain recording evoked movement corresponding limb. Thus, demonstrate functionally expressed different it important brain, laying ground further mechanistic studies ultrasound.

Language: Английский

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Ultrasound: A new strategy for artificial synapses modulation

InfoMat, Journal Year: 2024, Volume and Issue: 6(6)

Published: Feb. 27, 2024

Abstract Due to its non‐invasive nature, ultrasound has been widely used for neuromodulation in biological systems, where application influences the synaptic weights and process of neurotransmitter delivery. However, such modulation not emulated physical devices. Memristors are ideal electrical components artificial synapses, but up till now they hardly reported respond signals. Here we design fabricate a HfO x ‐based memristor on 64°Y‐X LiNbO 3 single crystal substrate, successfully realize synapses by shear‐horizontal surface acoustic wave (SH‐SAW). It is prominent short‐term resistance modulation, shown cause drop various states, which could fully recover after shut off. The mechanism illustrates that induced polarization potential dielectric layer acts Schottky barrier, leading drop. emulation neuron firing frequency through signals demonstrated. Moreover, joint electric voltage yields fruitful functionalities, as enhancement window plasticity application. All these promising results provide new strategy also further advance neuromorphic devices toward system applications. image

Language: Английский

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PIEZO Ion Channels in Cardiovascular Functions and Diseases

Circulation Research, Journal Year: 2024, Volume and Issue: 134(5), P. 572 - 591

Published: Feb. 29, 2024

The cardiovascular system provides blood supply throughout the body and as such is perpetually applying mechanical forces to cells tissues. Thus, this primed with mechanosensory structures that respond adapt changes in stimuli. Since their discovery 2010, PIEZO ion channels have dominated field of mechanobiology. These been proposed long-sought-after mechanosensitive excitatory involved touch proprioception mammals. However, more pieces evidence point importance activities disease development. channel-related cardiac functions include transducing hemodynamic endothelial vascular cells, red cell homeostasis, platelet aggregation, arterial pressure regulation, among others. contribute pathological conditions including hypertrophy pulmonary hypertension congenital syndromes generalized lymphatic dysplasia xerocytosis. In review, we highlight recent advances understanding role diseases. Achievements quickly expanding should open a new road for efficient control PIEZO-related diseases functions.

Language: Английский

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