title: Detection of bidirectional signaling during integrin activation and neutrophil adhesion.
abstract: Neutrophil arrest and migration on inflamed endothelium is dependent upon a conformational shift in CD11a/CD18 (LFA-1) from a low to high affinity and clustered state which determines the strength and lifetime of bond formation with intracellular adhesion molecule 1 (ICAM-1). Cytoskeletal adaptor proteins kindlin-3 and talin-1 anchor clustered LFA-1 to the cytoskeleton and support the transition from neutrophil rolling to arrest. We employ microfluidic flow channels and total internal reflection fluorescence microscopy to evaluate the spatiotemporal regulation of LFA-1 affinity and bond formation that facilitate the transition from neutrophil rolling to arrest. Methodology is presented to correlate the relationship between integrin conformation, bond formation with ICAM-1, and cytoskeletal engagement and adhesion strengthening necessary to achieve a migratory phenotype.
authors: Department of Biomedical Engineering, University of California, Davis, CA, USA.
authors: Stuart M
authors: SM
authors: Altman
authors: Neha
authors: N
authors: Dixit
authors: Scott I
authors: SI
authors: Simon
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D015815:Cell Adhesion Molecules; D016023:Integrins