A5057324568- Cellular Mechanics and Interactions
- Force Microscopy Techniques and Applications
- Analytic Number Theory Research
- Cardiomyopathy and Myosin Studies
- Cell Adhesion Molecules Research
- Advanced Algebra and Geometry
- Advanced Mathematical Identities
- 3D Printing in Biomedical Research
- Advanced Fluorescence Microscopy Techniques
- Microtubule and mitosis dynamics
- Molecular Junctions and Nanostructures
- Hippo pathway signaling and YAP/TAZ
- Advanced Electron Microscopy Techniques and Applications
- Tendon Structure and Treatment
- Pluripotent Stem Cells Research
- Algebraic Geometry and Number Theory
- RNA Research and Splicing
- Genetics, Aging, and Longevity in Model Organisms
- CAR-T cell therapy research
- Skin and Cellular Biology Research
- Micro and Nano Robotics
- Microfluidic and Bio-sensing Technologies
- Erythrocyte Function and Pathophysiology
- Mechanical and Optical Resonators
- Metal-Catalyzed Oxygenation Mechanisms
Stanford University
2016-2025
Royal North Shore Hospital
2025
Palo Alto University
2022-2024
Georgia Institute of Technology
2024
Cardiovascular Institute of the South
2013-2023
Health Promotion Agency
2022
University of Cambridge
2022
Stanford Medicine
2007-2021
University of California, Berkeley
2020-2021
University of Illinois Urbana-Champaign
2017-2020
Pulling me apart only makes stronger Tension transmitted between neighboring cells can exert profound effects on cell proliferation, differentiation, and tissue organization. Exactly how intercellular mechanical tension is sensed at the molecular level unknown. One attractive hypothesis that a linkage cell-cell adhesion molecule E-cadherin, its binding partners α- β-catenin, actin filaments may act as sensor. However, this established not known. Buckley et al. used optical tweezers to...
Classical cadherins are transmembrane proteins at the core of intercellular adhesion complexes in cohesive metazoan tissues. The extracellular domain classical forms bonds with on neighboring cells, whereas cytoplasmic recruits catenins, which turn associate additional cytoskeleton binding and regulatory proteins. Cadherin/catenin hypothesized to play a role transduction mechanical forces that shape cells tissues during development, regeneration, disease. Whether transduced directly through...
Abstract Insufficient reactivity against cells with low antigen density has emerged as an important cause of chimeric receptor (CAR) T-cell resistance. Little is known about factors that modulate the threshold for recognition. We demonstrate CD19 CAR activity dependent upon and construct in axicabtagene ciloleucel (CD19-CD28ζ) outperforms tisagenlecleucel (CD19-4-1BBζ) antigen-low tumors. Enhancing signal strength by including additional immunoreceptor tyrosine-based activation motifs (ITAM)...
Making the right catch Tension reveals cryptic vinculin-binding sites on α-catenin and talin at cadherin-based cell-cell integrin-based cell-matrix adhesions, respectively. The enrichment of vinculin cellular adhesions is thus an indicator load-induced reinforcement cytoskeletal linkage. Huang et al. used a single-molecule optical trap assay to measure binding lifetimes single actin filaments under load. vinculin-F-actin interaction formed directional bond—one that very weak low force but...
Living cells are exquisitely responsive to mechanical cues, yet how produce and detect force remains poorly understood due a lack of methods that visualize cell-generated forces at the molecular scale. Here we describe Förster resonance energy transfer (FRET)-based tension sensors allow us directly with single-molecule sensitivity. We apply these determine distribution generated by individual integrins, class cell adhesion molecules prominent roles throughout developmental biology. observe...
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
Metastasis requires tumor cells to navigate through a stiff stroma and squeeze confined microenvironments. Whether tumors exploit unique biophysical properties metastasize remains unclear. Data show that invading mammary cells, when cultured in stiffened three-dimensional extracellular matrix recapitulates the primary stroma, adopt basal-like phenotype. Metastatic exert higher integrin-mediated traction forces at bulk molecular levels, consistent with motor-clutch model which motors clutches...
Although mechanical stress is known to profoundly influence the composition and structure of extracellular matrix (ECM), mechanisms by which this regulation occurs remain poorly understood. We used a single-molecule magnetic tweezers assay study effect force on collagen proteolysis metalloproteinase-1 (MMP-1). Here we show that application ∼10 pN in extensional causes an ∼100-fold increase rates. Our results support mechanistic model triple helix unwinds prior proteolysis. The data resulting...
Our bodies are in constant motion and so the neurons that invade each tissue. Motion-induced neuron deformation damage associated with several neurodegenerative conditions. Here, we investigated question of how neuronal cytoskeleton protects axons dendrites from mechanical stress, exploiting mutations UNC-70 β-spectrin, PTL-1 tau/MAP2-like MEC-7 β-tubulin proteins Caenorhabditis elegans. We found stress induces supercoils plectonemes sensory spectrin tau double mutants. Biophysical...
Integrins mediate cell adhesion to the extracellular matrix and enable construction of complex, multicellular organisms, yet fundamental aspects integrin-based remain poorly understood. Notably, magnitude mechanical load experienced by individual integrins within living cells is unclear, due principally limitations inherent existing techniques. Here we use Förster resonance energy transfer-based molecular tension sensors directly measure distribution loads in cells. We find that a large...
Sufficient blood flow to tissues relies on arterial vessels, but the mechanisms regulating their development are poorly understood. Many arteries, including coronary arteries of heart, form through remodeling an immature vascular plexus in a process triggered and shaped by flow. However, little is known about how cues from fluid shear stress translated into responses that pattern artery development. Here, we show mice lacking endothelial Dach1 had small decreased cell polarization, reduced...
Desmosomes are intercellular adhesion complexes that connect the intermediate filament cytoskeletons of neighboring cells, and essential for mechanical integrity mammalian tissues. Mutations in desmosomal proteins cause severe human pathologies including epithelial blistering heart muscle dysfunction. However, direct evidence their load-bearing nature is lacking. Here we develop Förster resonance energy transfer (FRET)-based tension sensors to measure forces experienced by desmoplakin, an...
Focal adhesions (FAs) are micron-sized protein assemblies that coordinate cell adhesion, migration, and mechanotransduction. How the many proteins within FAs organized into force sensing transmitting structures is poorly understood. We combined fluorescent molecular tension sensors with super-resolution light microscopy to visualize traction forces <100 nm spatial resolution. find αvβ3 integrin selectively localizes high regions. Paxillin, which not generally considered play a direct role in...
Integrin-based adhesion complexes link the cytoskeleton to extracellular matrix (ECM) and are central construction of multicellular animal tissues. How biological function emerges from tens thousands proteins present within a single complex remains unclear. We used fluorescent molecular tension sensors visualize force transmission by individual integrins in living cells. These measurements revealed an underlying functional modularity which integrin class controlled size ECM ligand...
Significance Talin is a mechanosensitive adaptor protein that links integrins to the actin cytoskeleton at cell–extracellular matrix adhesions. Although C-terminal actin-binding domain ABS3 of talin required for function, it binds weakly in solution. We show strongly only when subjected mechanical forces comparable those generated by cytoskeleton. Moreover, interaction between and depends on direction force manner predicted organize facilitate adhesion growth efficient cytoskeletal...
Mechanotransduction at cell–cell adhesions is crucial for the structural integrity, organization, and morphogenesis of epithelia. At junctions, ternary E-cadherin/β-catenin/αE-catenin complexes sense transmit mechanical load by binding to F-actin. The interaction with F-actin, described as a two-state catch bond, weak in solution but strengthened applied force due force-dependent transitions between strong actin-binding states. Here, we provide direct evidence from optical trapping...
Abstract The development of high-resolution microscopes has made it possible to investigate cellular processes in 3D and over time. However, observing fast dynamics remains challenging because photobleaching phototoxicity. Here we report the implementation two content-aware frame interpolation (CAFI) deep learning networks, Zooming SlowMo Depth-Aware Video Frame Interpolation, that are highly suited for accurately predicting images between image pairs, therefore improving temporal resolution...