A5076168640- Cellular Mechanics and Interactions
- Force Microscopy Techniques and Applications
- 3D Printing in Biomedical Research
- Hearing, Cochlea, Tinnitus, Genetics
- Hearing Loss and Rehabilitation
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Heat shock proteins research
- Microtubule and mitosis dynamics
- Barrier Structure and Function Studies
- Cancer Cells and Metastasis
- thermodynamics and calorimetric analyses
- Tendon Structure and Treatment
- Mechanical and Optical Resonators
- Cellular transport and secretion
- Immunotherapy and Immune Responses
- Spaceflight effects on biology
- CAR-T cell therapy research
- Bone Tissue Engineering Materials
- Neuroscience and Neural Engineering
- Cell Image Analysis Techniques
- Microfluidic and Bio-sensing Technologies
- Advanced Materials and Mechanics
- Acoustic Wave Phenomena Research
- Hippo pathway signaling and YAP/TAZ
National Institutes of Health
2016-2025
National Institute of Biomedical Imaging and Bioengineering
2020-2024
National Institute on Deafness and Other Communication Disorders
2015-2019
Purdue University West Lafayette
2015-2019
National Heart Lung and Blood Institute
2016
Abstract Defining the principles of T cell migration in structurally and mechanically complex tumor microenvironments is critical to understanding escape from antitumor immunity optimizing cell-related therapeutic strategies. Here, we engineered nanotextured elastic platforms study enhance through define how balance between contractility localization-dependent phenotypes influences response tumor-mimetic structural mechanical cues. Using these platforms, characterize a optimum for that can...
Within the confines of tissues, cancer cells can use blebs to migrate. Eps8 is an actin bundling and capping protein whose activity inhibited by Erk, a key MAP kinase that activated oncogenic signaling. We tested hypothesis acts as Erk effector modulate cortex mechanics thereby mediate bleb-based migration cells. Cells confined in non-adhesive environment migrate direction very large ‘leader bleb.’ promotes tension intracellular pressure drive leader bleb formation. activities act...
The organization of filamentous actin and myosin II molecular motor contractility is known to modify the mechanical properties cell cortical actomyosin cytoskeleton. Here we describe a novel method, our knowledge, for using force spectroscopy approach curves with tipless cantilevers determine tension, elastic modulus, intracellular pressure nonadherent cells. We validated method by measuring surface tension water in oil microdrops deposited on glass surface. extracted an average T ∼ 20.25...
A longstanding goal in cellular mechanobiology has been to link dynamic biomolecular processes underpinning disease or morphogenesis spatio-temporal changes nanoscale mechanical properties such as viscoelasticity, surface tension, and adhesion. This requires the development of quantitative microscopy methods with high resolution within a single cell. The Atomic Force Microscope (AFM) can map heterogeneous cells spatial resolution, however, image acquisition time is 1-2 orders magnitude...
Many embryonic organs undergo epithelial morphogenesis to form tree-like hierarchical structures. However, it remains unclear what drives the budding and branching of stratified epithelia, such as in salivary gland pancreas. Here, we performed live-organ imaging mouse glands at single-cell resolution reveal that is driven by expansion folding a distinct surface cell sheet characterized strong cell-matrix adhesions weak cell-cell adhesions. Profiling transcriptomes this epithelium revealed...
The all-terrain motility of lymphocytes in tissues and tissue-like gels is best described as amoeboid motility. For motility, do not require specific biochemical or structural modifications to the surrounding extracellular matrix. Instead, they rely on changing shape steric interactions with microenvironment. However, exact mechanism remains elusive. Here, we report that septins participate T cells, enabling formation F-actin α-actinin-rich cortical rings at sites cell cortex-indenting...
Electrostatics is one of the fundamental driving forces interaction between biomolecules in solution. In particular, recognition events viruses and host cells are dominated by both specific non-specific interactions electric charge viral particles determines electrostatic force component latter. Here we probe individual liquid milieu measuring a particle Atomic Force Microscope tip. The spectroscopy data co-adsorbed ϕ29 bacteriophage proheads mature virions, adenovirus minute virus mice...
Maintenance of epithelial tissue integrity requires coordination between cell-cell adherens junctions, tight junctions (TJ), and the perijunctional actomyosin cytoskeleton. Here we addressed hypothesis that alterations in TJ structure remodeling cytoskeleton modify mechanics. Current methods to measure supracellular mechanical properties disrupt intact monolayers, therefore, developed a novel method using noncontact acoustic frequency-modulation atomic force microscopy (FM-AFM) tested it on...
Abstract The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions, triggering mechanoresponses. However, it has been unclear if stiffness-dependent is induced solely by myosin activity. Here, we report that in absence contractility, 3T3 fibroblasts still transmit levels traction. This myosin-independent traction regulated polymerizing actin assisted nucleators Arp2/3 and formin where a stronger contribution than to both flow. Intriguingly,...
<title>Abstract</title> Tissue-level phase transitions are emerging as a crucial mechanism in tumour development and metastasis. This study aims to identify molecular determinants physical conditions that control active wetting solid-to-fluid transition of epithelial tissues. We focused on IRSp53, protein linking plasma membranes the cytoskeleton. Depleting MCF10 DCIS.com cells, disrupts coordinated collective movement by promoting local fluctuations cell velocity resulting increased tissue...
Cancer cell migration requires that cells respond and adapt to their surroundings. In the absence of extracellular matrix cues, cancer will undergo a mesenchymal ameboid transition, whereas highly confining space trigger switch "leader bleb-based" migration. To identify oncogenic signaling pathways mediating these transitions, we undertook targeted screen using clinically useful inhibitors. Elevated Src activity was found change actin focal adhesion dynamics, inhibiting triggered disassembly...
The conventional approaches to assess the potential cytotoxic effects of nanomaterials (NMs) mainly rely on in vitro biochemical assays. These assays are strongly dependent properties nanomaterials, for example; specific surface area (SSA), size, defects, and charge, host response. NMs can also interfere with reagents optical leading skewed interpretations ambiguous results related toxicity. Here, we proposed a structured approach cytotoxicity assessment complemented cells' mechanical...
TRIOBP remodels the cytoskeleton by forming unusually dense F-actin bundles and is implicated in human cancer, schizophrenia, deafness. Mutations ablating mouse TRIOBP-4 TRIOBP-5 isoforms are associated with profound deafness, as inner ear mechanosensory hair cells degenerate after stereocilia rootlets fail to develop. However, mechanisms regulating formation of each isoform remain unknown. Using 3 new Triobp models, we report that essential for thickening rootlets, establishing their mature...
Abstract Countless biophysical studies have sought distinct markers in the cellular mechanical response that could be linked to morphogenesis, homeostasis, and disease. Here, an iterative-fitting methodology visualizes time-dependent viscoelastic behavior of human skin cells under physiologically relevant conditions. Past investigations often involved parameterizing elastic relationships assuming purely Hertzian contact mechanics, which fails properly account for rich temporal information...
The actomyosin cytoskeleton serves as a key regulator of the integrity and remodeling epithelial barriers by controlling assembly functions intercellular junctions cell-matrix adhesions. Although biochemical mechanisms that regulate activity non-muscle myosin II (NM-II) in cells have been extensively investigated, little is known about contractile structures at adhesion sites. UNC-45A cytoskeletal chaperone essential for proper folding NM-II heavy chains myofilament assembly. We found...
Although the actomyosin cytoskeleton has been implicated in clathrin-mediated endocytosis, a clear requirement for clathrin-independent endocytosis (CIE) not demonstrated. We discovered that Rho-associated kinase ROCK2 is required CIE of MHCI and CD59 through promotion myosin II activity. Myosin IIA promoted internalization IIB drove uptake both HeLa polarized Caco2 intestinal epithelial cells. In cells, localized to basal cortex apical brush border mediated from basolateral domain, while at...
Microtubules (MTs) and MT motor proteins form active 3D networks made of unstretchable cables with rod-like bending mechanics that provide cells a dynamically changing structural scaffold. In this study, we report an antagonistic mechanical balance within the dynein-kinesin microtubular system. Dynein activity drives network inward compaction, while isolated kinesins bundles expands MTs into giant circular bands deform cell cortex discoids. Furthermore, show dyneins recruit to sites...
Outer hair cell (OHC) stereocilia bundle deflection opens mechanoelectrical transduction channels at the tips of from middle and short rows, while cohesion is maintained owing to presence horizontal top connectors. Here, we used a quantitative noncontact atomic force microscopy method investigate stiffness damping, when stimulated acoustic frequencies nanometer distances bundle. Stereocilia mechanics were determined in stereocilin-deficient mice lacking connectors with detached tectorial...
Cancer cells migrating in confined microenvironments exhibit plasticity of migration modes. Confinement contractile a nonadhesive environment drives "leader bleb-based migration" (LBBM), morphologically characterized by long bleb that points the direction movement separated from cell body neck. Although undergoing LBBM have been visualized within tumors, organization organelles and actin regulatory proteins mediating is unknown. We analyzed localization fluorescent organelle-specific markers...
Hearing loss is a common disorder affecting nearly 20% of the world's population. Recently, studies have shown that inner ear gene therapy can improve auditory function in several mouse models hereditary hearing loss. In most these studies, underlying mutations affect only small number cell types (e.g., sensory hair cells). Here, we applied to Ildr1