A5036800314- Cell Adhesion Molecules Research
- Force Microscopy Techniques and Applications
- Cellular Mechanics and Interactions
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Platelet Disorders and Treatments
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Glycosylation and Glycoproteins Research
- Blood properties and coagulation
- Biochemical and Structural Characterization
- Lipid Membrane Structure and Behavior
- Geology and Paleoclimatology Research
- Blood groups and transfusion
- Mechanical and Optical Resonators
- Nanofabrication and Lithography Techniques
- Advanced Multi-Objective Optimization Algorithms
- Receptor Mechanisms and Signaling
- Immune Response and Inflammation
- Blockchain Technology Applications and Security
- Direction-of-Arrival Estimation Techniques
- Radio Wave Propagation Studies
- Cancer Immunotherapy and Biomarkers
- Gaussian Processes and Bayesian Inference
Georgia Institute of Technology
2016-2025
The Wallace H. Coulter Department of Biomedical Engineering
2014-2025
Shanghai Ninth People's Hospital
2025
Shanghai Jiao Tong University
2021-2025
University of Southampton Malaysia
2025
National University of Defense Technology
2014-2024
Parker Hannifin (United States)
2022-2024
First Affiliated Hospital of Anhui Medical University
2021-2023
Anhui Medical University
2021-2023
Sanofi (United States)
2021-2023
Binding of integrins to ligands provides anchorage and signals for the cell, making them prime candidates mechanosensing molecules. How force regulates integrin–ligand dissociation is unclear. We used atomic microscopy measure force-dependent lifetimes single bonds between a fibronectin fragment an integrin α5β1-Fc fusion protein or membrane α5β1. Force prolonged bond in 10–30-pN range, counterintuitive behavior called catch bonds. Changing cations from Ca2+/Mg2+ Mg2+/EGTA Mn2+ caused longer...
Arterial blood flow enhances glycoprotein Ibα (GPIbα) binding to vWF, which initiates platelet adhesion injured vessels. Mutations in the vWF A1 domain that cause type 2B von Willebrand disease (vWD) reduce requirement for adhesion. Here we show increasing force on GPIbα/vWF bonds first prolonged ("catch") and then shortened ("slip") bond lifetimes. Two vWD mutants, R1306Q R1450E, converted catch slip by prolonging lifetimes at low forces. Steered molecular dynamics simulations of GPIbα...
Forces on Notch receptors can modulate receptor signaling.
Many biomolecular bonds exhibit a mechanical strength that increases in proportion to the logarithm of rate force application. Consistent with exponential decrease bond lifetime under rising force, this kinetically limited failure reflects dissociation along single thermodynamic pathway impeded by sharp free energy barrier. Using sensitive probe test leukocyte adhesion P-selectin glycoprotein ligand 1 (PSGL-1)–P-selectin, we observed linear increase each 10-fold application from 300 30,000...
Selectin-ligand interactions mediate the tethering and rolling of circulating leukocytes on vascular surfaces during inflammation immune surveillance. To support rolling, these are thought to have rapid off-rates that increase slowly as wall shear stress increases. However, off-rate with force, an intuitive characteristic named slip bonds, is at odds a threshold requirement for selectin-mediated cell rolling. As drops below threshold, fewer cells roll those do less stably higher velocity. We...
Flow-enhanced cell adhesion is an unexplained phenomenon that might result from a transport-dependent increase in on-rates or force-dependent decrease off-rates of adhesive bonds. L-selectin requires threshold shear to support leukocyte rolling on P-selectin glycoprotein ligand-1 (PSGL-1) and other vascular ligands. Low forces L-selectin–PSGL-1 (catch bonds), whereas higher (slip bonds). We determined dictated flow-enhanced L-selectin–bearing microspheres neutrophils PSGL-1. Catch bonds...
Binding of lymphocyte function-associated antigen-1 (LFA-1) to intercellular adhesion molecule-1 (ICAM-1) mediates leukocyte under force. Using a biomembrane force probe capable measuring single bond interactions, we showed ICAM-1 binding LFA-1 at different conformations, including the bent conformation with lowest affinity. We quantify how and conformations regulate its kinetics ICAM-1. At zero-force, on-rates were substantially changed by conditions that differentially favor or extended...
T cell affinity for antigen initiates adaptive immunity. However, the contribution of low cells to a response is unknown as it has not been possible assess entire range polyclonal repertoire. In this study, we used highly sensitive two-dimensional binding assay identify in autoreactive and pathogen-reactive CD4+ populations specific myelin oligodendrocyte glycoprotein (MOG) lymphocytic choriomeningitis virus (LCMV) antigens, respectively. Low cells, below detection with peptide–major...
As adhesion molecules, integrins connect a cell to its environment and transduce signals across the membrane. Their different functional states correspond distinct conformations. Using biomembrane force probe, we observed real-time reversible switches between bent extended conformations of single integrin, αLβ2, on surface living by measuring nanometer-scale headpiece displacements, bending unbending frequencies, molecular stiffness changes. We determined stabilities these conformations,...
The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development autoimmunity. However, mechanisms that allow clonal cell antigen receptor (TCR) to functionally engage multiple peptide–major histocompatibility complexes (pMHC) are unclear. Here, we studied multiligand discrimination by human, preproinsulin reactive, MHC class-I–restricted CD8+ clone (1E6) can recognize over 1 million different peptides. We generated...