A5003753703- Erythrocyte Function and Pathophysiology
- Ion channel regulation and function
- Cellular Mechanics and Interactions
- Blood properties and coagulation
- Cardiac electrophysiology and arrhythmias
- Superconducting Materials and Applications
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- 3D Printing in Biomedical Research
- Planarian Biology and Electrostimulation
- Lipid Membrane Structure and Behavior
- Microtubule and mitosis dynamics
- Economic Growth and Productivity
- Ferroelectric and Negative Capacitance Devices
- Microfluidic and Bio-sensing Technologies
- Phagocytosis and Immune Regulation
- Photoreceptor and optogenetics research
- Fuel Cells and Related Materials
- Plant and Biological Electrophysiology Studies
- Cell Adhesion Molecules Research
- Caveolin-1 and cellular processes
- Semiconductor materials and devices
- Nanopore and Nanochannel Transport Studies
- Cephalopods and Marine Biology
- Neurogenesis and neuroplasticity mechanisms
University of California, Irvine
2016-2025
UC Irvine Health
2018-2022
ORCID
2022
University of California, Berkeley
2004-2007
Harvard University
2006
Neural stem cells are multipotent with the ability to differentiate into neurons, astrocytes, and oligodendrocytes. Lineage specification is strongly sensitive mechanical properties of cellular environment. However, molecular pathways transducing matrix cues intracellular signaling linked lineage remain unclear. We found that mechanically gated ion channel Piezo1 expressed by brain-derived human neural stem/progenitor responsible for a induced ionic current. activity triggered traction...
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,...
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
Keratinocytes, the predominant cell type of epidermis, migrate to reinstate epithelial barrier during wound healing. Mechanical cues are known regulate keratinocyte re-epithelialization and healing; however, underlying molecular transducers biophysical mechanisms remain elusive. Here, we show through molecular, cellular, organismal studies that mechanically activated ion channel PIEZO1 regulates migration Epidermal-specific Piezo1 knockout mice exhibited faster closure while gain-of-function...
Human neural stem/progenitor cells (hNSPCs) are good candidates for treating central nervous system (CNS) trauma since they secrete beneficial trophic factors and differentiate into mature CNS cells; however, many die after transplantation. This cell death can be ameliorated by inclusion of a biomaterial scaffold, making identification optimal scaffolds hNSPCs critical research focus. We investigated the properties fibrin-based their effects on found that fibrin generated from salmon...
Mechanosensitive Piezo1 channels restrict regulatory T cell expansion and limit disease remission in EAE.
Piezo1 is a bona fide mechanosensitive ion channel ubiquitously expressed in mammalian cells. The distribution of within cell essential for various biological processes including cytokinesis, migration, and wound healing. However, the underlying principles that guide subcellular remain largely unexplored. Here, we demonstrate membrane curvature serves as key regulator spatial plasma living depletes from highly curved protrusions such filopodia enriches to nanoscale invaginations....
The four arginine-rich S4 helices of a voltage-gated channel move outward through the membrane in response to depolarization, opening and closing gates generate transient ionic current. Coupling voltage sensing gating was originally thought operate with S4s moving independently from an inward/resting outward/activated conformation, so that when all are activated, driven open or closed. However, has also been found influence cooperative step (Smith-Maxwell et al., 1998a), suggesting more...
SummaryVoltage-gated sodium, potassium, and calcium channels are made of a pore domain (PD) controlled by four voltage-sensing domains (VSDs). The PD contains the ion permeation pathway activation gate located on intracellular side membrane. A large number small molecules known to inhibit acting as open channel blockers. voltage-gated proton Hv1 is two VSDs lacks PD. location in VSD unknown blockers for have not yet been identified. Here, we describe class which act find that highly...
Abstract Neural stem and progenitor cell (NSPC) fate is strongly influenced by mechanotransduction as modulation of substrate stiffness affects lineage choice. Other types mechanical stimuli, such stretch (tensile strain), occur during CNS development trauma, but their consequences for NSPC differentiation have not been reported. We delivered a 10% static equibiaxial to NSPCs examined effects on differentiation. found specifically impacts into oligodendrocytes, neurons or astrocytes this...
Macrophages are versatile cells of the innate immune system that perform diverse functions by responding to dynamic changes in their microenvironment. While effects soluble cues, including cytokines and chemokines, have been widely studied, physical mechanical stimuli, regulating macrophage form function less well understood. In this study, we examined static cyclic uniaxial stretch on inflammatory healing activation. We found altered morphology responses IFNγ/LPS IL4/IL13. Interestingly,...
The collective migration of keratinocytes during wound healing requires both the generation and transmission mechanical forces for individual cellular locomotion coordination movement across cells. Leader cells along edge transmit biochemical cues to ensuing follower cells, ensuring their coordinated direction multiple Despite observed importance in leader cell formation controlling directionality migration, underlying biophysical mechanisms remain elusive. mechanically-activated ion channel...
Adipocytes function as an energy buffer and undergo significant size volume changes in response to nutritional cues. This adipocyte plasticity is important for systemic lipid metabolism insulin sensitivity. Accompanying the changes, mechanical pressure against cell membrane also changes. However, role that plays sensitivity remains be elucidated. Here we show Piezo1, a mechanically-activated cation channel stimulated by tension stretch, was highly expressed adipocytes. Adipose Piezo1...
Mechanical forces and tissue mechanics influence the morphology of developing brain, but underlying molecular mechanisms have been elusive. Here, we examine role mechanotransduction in brain development by focusing on Piezo1, a mechanically activated ion channel. We find that Piezo1 deletion results thinner neuroepithelial layer, disrupts pseudostratification, reduces neurogenesis E10.5 mouse embryos. Proliferation differentiation knockout (KO) neural stem cells (NSCs) isolated from embryos...
The mechanically-activated ion channel PIEZO1 is critical to numerous physiological processes, and activated by diverse mechanical cues. gated membrane tension has been found be mobile in the plasma membrane. We employed single particle tracking (SPT) of endogenous, tdTomato-tagged using Total Internal Reflection Fluorescence Microscopy live cells. Application SPT unveiled a surprising heterogeneity diffusing subpopulations, which we labeled "mobile" "immobile". sorted these trajectories...
Abstract Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing more committed progenitors that differentiate into neurons, astrocytes, oligodendrocytes. Accurately identifying characterizing the different in this lineage has continued to be a challenge for field. We found previously NSPCs with neurogenic (NPs) can distinguished from those astrogenic (APs) by their inherent biophysical properties, specifically electrophysiological property whole cell membrane...
The voltage-gated proton channel, Hv1, is expressed in tissues throughout the body and plays important roles pH homeostasis regulation of NADPH oxidase. Hv1 operates membrane compartments that experience strong mechanical forces under physiological or pathological conditions. In microglia, for example, activity potentiated by cell swelling causes an increase brain damage after stroke. channel complex consists two proton-permeable voltage-sensing domains (VSDs) linked a cytoplasmic...