Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Epublish 4 citations
PubMed: 36139397 DOI: 10.3390/cells11182822
β-Integrin Adhesive Bond Tension under Shear Stress Modulates Cytosolic Calcium Flux and Neutrophil Inflammatory Response.
Cells 11(18)
Authors: Vasilios Aris Morikis, Szu Jung Chen, Julianna Madigan, Myung Hyun Jo, Lisette Caroline Werba, Taekjip Ha, Scott Irwin Simon
Affiliations
- Department of Biomedical Engineering, University of California-Davis, Davis, CA 95616, USA.
- Department of Biophysics & Biophysical Chemistry, Baltimore, MD 21218, USA.
- Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Abstract
On arrested neutrophils a focal adhesive cluster of ~200 high affinity (HA) β-integrin bonds under tension is sufficient to trigger Ca flux that signals an increase in activation in direct proportion to increments in shear stress. We reasoned that a threshold tension acting on individual β-integrin bonds provides a mechanical means of transducing the magnitude of fluid drag force into signals that enhance the efficiency of neutrophil recruitment and effector function. Tension gauge tethers (TGT) are a duplex of DNA nucleotides that rupture at a precise shear force, which increases with the extent of nucleotide overlap, ranging from a tolerance of 54pN to 12pN. TGT annealed to a substrate captures neutrophils via allosteric antibodies that stabilize LFA-1 in a high- or low-affinity conformation. Neutrophils sheared on TGT substrates were recorded in real time to form HA β-integrin bonds and flux cytosolic Ca, which elicited shape change and downstream production of reactive oxygen species. A threshold force of 33pN triggered consolidation of HA β-integrin bonds and triggered membrane influx of Ca, whereas an optimum tension of 54pN efficiently transduced activation at a level equivalent to chemotactic stimulation on ICAM-1. We conclude that neutrophils sense the level of fluid drag transduced through individual β-integrin bonds, providing an intrinsic means to modulate inflammatory response in the microcirculation.
MeSH
Integrins, Stress, Physiological, Cells, Calcium, Neutrophils, Adhesives