A5019253861- Cellular Mechanics and Interactions
- Force Microscopy Techniques and Applications
- Wnt/β-catenin signaling in development and cancer
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Nanofabrication and Lithography Techniques
- Advanced Fluorescence Microscopy Techniques
- Skin and Cellular Biology Research
- Near-Field Optical Microscopy
- Mechanical and Optical Resonators
- Protein Structure and Dynamics
- Optical Imaging and Spectroscopy Techniques
- Biotin and Related Studies
- Quantum Dots Synthesis And Properties
- HER2/EGFR in Cancer Research
- Chalcogenide Semiconductor Thin Films
- Adhesion, Friction, and Surface Interactions
- Molecular Junctions and Nanostructures
- Click Chemistry and Applications
- Toxin Mechanisms and Immunotoxins
- Microstructure and mechanical properties
- Lipid Membrane Structure and Behavior
- Prion Diseases and Protein Misfolding
- Trace Elements in Health
- Heat Transfer Mechanisms
University of California, Davis
2018-2025
SRM Institute of Science and Technology
2014-2024
Indiana University – Purdue University Indianapolis
2020
Iowa State University
2009-2018
Ames National Laboratory
2010-2016
United States Department of Energy
2009-2014
Lawrence Berkeley National Laboratory
2007-2009
Material Sciences (United States)
2009
University of California, Berkeley
2007-2009
Stanford University
2007
Classical cadherin cell-cell adhesion proteins play key morphogenetic roles during development and are essential for maintaining tissue integrity in multicellular organisms. cadherins bind two distinct conformations, X-dimer strand-swap dimer; cellular rearrangements, these adhesive states exposed to mechanical stress. However, the molecular mechanisms by which resist tensile force pathway they convert between different conformations unclear. Here, we use single molecule measurements with an...
The cadherin family of Ca 2+ -dependent cell adhesion proteins are critical for the morphogenesis and functional organization tissues in multicellular organisms, but molecular interactions between cadherins that at core cell–cell a matter considerable debate. A widely-accepted model is adhere 3 stages. First, unit cis dimer formed by binding extracellular regions 2 on same surface. Second, formation low-affinity trans dimers opposing surfaces initiates adhesion. Third, lateral clustering...
Direct-force measurements of the interactions between recombinant C-cadherin from Xenopus demonstrated that ectodomain cadherin exhibits multiple adhesive contacts involve successive domains along extracellular region protein. Contacts fully interdigitated antiparallel proteins form strongest interaction. A second weaker minimum was measured when were separated by a distance equal to length one domain (EC) fragment and corresponding alignment through four (EC1 EC4). The rupture these...
The photoluminescence of CdSe/CdS core/shell quantum dots, nanorods, and tetrapods is investigated as a function applied hydrostatic non-hydrostatic pressure. optoelectronic properties all three nanocrystal morphologies are affected by strain. Furthermore, it demonstrated that the unique morphology seeded highly sensitive to non-isotropic stress environments. Seeded can thereby serve an optical strain gauge, capable measuring forces on order nanonewtons. We anticipate gauge with readout will...
Desmosomes are adhesive junctions composed of two desmosomal cadherins: desmocollin (Dsc) and desmoglein (Dsg). Previous studies demonstrate that E-cadherin (Ecad), an protein interacts in both trans (between opposing cells) cis (on the same cell surface) conformations, facilitates desmosome assembly via unknown mechanism. Here we use structure-function analysis to resolve mechanistic roles Ecad formation. Using AFM force measurements, with isoform 2 Dsg a conserved Leu-175 on binding...
Abstract Fluorescence correlation spectroscopy (FCS), is a widely used tool routinely exploited for in vivo and vitro applications. While FCS provides estimates of dynamical quantities, such as diffusion coefficients, it demands high signal to noise ratios long time traces, typically the minute range. In principle, same information can be extracted from microseconds seconds traces; however, an appropriate analysis method missing. To overcome these limitations, we adapt novel tools inspired...
Adhesion between cells is established by the formation of specialized intercellular junctional complexes, such as desmosomes. Desmosomes comprise two members cadherin superfamily cell adhesion proteins, desmocollin (Dsc) and desmoglein (Dsg), but their combinatorial roles in desmosome assembly not understood. To uncouple from other cell-cell we used micro-patterned substrates Dsc2aFc and/or Dsg2Fc collagen IV; show that Dsc2aFc, Dsg2Fc, was necessary sufficient to recruit desmosome-specific...
Desmosomes are adhesive cell contacts abundant in tissues exposed to mechanical strain, such as the stratified and simple epithelia of epidermis mucous membranes, well myocardium. Besides their role cohesion, desmosomes also modulate pathways important for tissue differentiation, wound healing immune responses. Dysfunctional desmosomes, resulting from pathogenic variants genes encoding desmosomal components, autoantibodies targeting adhesion molecules or inflammation, cause life-threatening...
Copper induces prion protein misfolding, aggregation, and neurotoxicity.
Fluorescence time traces are used to report on dynamical properties of molecules. The basic unit information in these is the arrival individual photons, which carry instantaneous from molecule, they emitted, detector timescales as fast microseconds. Thus, it theoretically possible monitor molecular dynamics at such containing only a sufficient number photon arrivals. In practice, however, stochastic and order deduce through traditional means—such fluorescence correlation spectroscopy (FCS)...
Significance Cadherin cell–cell adhesion proteins play key roles in the formation and maintenance of tissues. Their is carefully regulated to orchestrate complex movement cells. While cadherin ectodomains bind two conformations with different adhesive properties, mechanisms by which cells regulate conformation (and consequently adhesion) individual cadherins are unknown. Here, we demonstrate that association intracellular vinculin cytoplasmic region regulates switching from a weak binding...
In this work, we used direct measurements with the surface force apparatus to determine pH-dependent electrostatic charge density of a single binding face streptavidin. Mean field calculations have been considerable success model potential fields near protein surfaces, but these models and their inherent assumptions not tested directly at molecular level. Using immobilized, oriented monolayers streptavidin, measured pI 5–5.5 for biotin-binding protein. This differs from 6.3 soluble confirms...
Recent advances in the synthesis of multicomponent nanocrystals have enabled design nanocrystal molecules with unique photophysical behavior and functionality. Here we demonstrate a highly luminescent molecule, CdSe/CdS core/shell tetrapod, which is designed to weak vibronic coupling between excited states thereby violates Kasha's rule via emission from multiple levels. Using single particle photoluminescence spectroscopy, show that addition expected LUMO HOMO radiative transition, higher...
Significance While transmembrane proteins are essential for cellular function, it is extremely challenging to identify their interactions using traditional biochemical methods. Here we combine proximity labeling and single molecule binding assays discover protein in cells. We initially screen that located proximal a of interest (the “bait”), by tagging both the extracellular cytoplasmic regions bait with enzyme, BioID. then directly test between atomic force microscopy. Using this approach,...
Significance Multicellular assemblies rely on the robust binding of classical cadherin cell–cell adhesion proteins to maintain their integrity and withstand mechanical stress. Cadherins can form adhesive interactions that are insensitive tugging forces; however, biophysical mechanism for force insensitivity is unknown. Here, we integrate single-molecule measurements with computer simulations show cadherins, which known bind in two distinct conformations, adopt an intermediate structure as...
ABSTRACT Proximity labeling with genetically encoded enzymes is widely used to study protein–protein interactions in cells. However, the accuracy of proximity limited by a lack control over enzymatic process. Here, we present light-activated technology for mapping at cell membrane high and precision. Our technology, called BioID (LAB), fuses two halves split-TurboID enzyme photodimeric proteins CRY2 CIB1. We demonstrate, multiple lines, that upon illumination blue light, CIB1 dimerize,...
Abstract P-cadherin, a crucial cell-cell adhesion protein which is overexpressed in numerous malignant cancers, popular target for drug delivery antibodies. However, molecular guidelines engineering antibodies that can be internalized upon binding to P-cadherin are unknown. Here, we use combination of biophysical, biochemical, and cell biological methods demonstrate trapping the extracellular region an X-dimer adhesive conformation triggers cadherin endocytosis via outside-in signaling...