title: An analytical model for determining two-dimensional receptor-ligand kinetics.
abstract: Cell-cell adhesive interactions play a pivotal role in major pathophysiological vascular processes, such as inflammation, infection, thrombosis, and cancer metastasis, and are regulated by hemodynamic forces generated by blood flow. Cell adhesion is mediated by the binding of receptors to ligands, which are both anchored on two-dimensional (2-D) membranes of apposing cells. Biophysical assays have been developed to determine the unstressed (no-force) 2-D affinity but fail to disclose its dependence on force. Here we develop an analytical model to estimate the 2-D kinetics of diverse receptor-ligand pairs as a function of force, including antibody-antigen, vascular selectin-ligand, and bacterial adhesin-ligand interactions. The model can account for multiple bond interactions necessary to mediate adhesion and resist detachment amid high hemodynamic forces. Using this model, we provide a generalized biophysical interpretation of the counterintuitive force-induced stabilization of cell rolling observed by a select subset of receptor-ligand pairs with specific intrinsic kinetic properties. This study enables us to understand how single-molecule and multibond biophysics modulate the macroscopic cell behavior in diverse pathophysiological processes.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences in Oncology Center, and Institute of NanoBioTechnology, The Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Luthur Siu-Lun
authors.initials: LS
authors.lastname: Cheung
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Konstantopoulos
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000941:Antigens / Q000378:metabolism; D001422:Bacterial Adhesion; D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D002465:Cell Movement; D019040:E-Selectin / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D019041:L-Selectin / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D019007:P-Selectin / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D013314:Stress, Mechanical
chemical_list: D000906:Antibodies; D000941:Antigens; D019040:E-Selectin; D016256:Lewis X Antigen; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D011956:Receptors, Cell Surface; D000080506:Sialyl Lewis X Antigen; D019041:L-Selectin