title: A Rough Energy Landscape to Describe Surface-Linked Antibody and Antigen Bond Formation.
abstract: Antibodies and B cell receptors often bind their antigen at cell-cell interface while both molecular species are surface-bound, which impacts bond kinetics and function. Despite the description of complex energy landscapes for dissociation kinetics which may also result in significantly different association kinetics, surface-bound molecule (2D) association kinetics usually remain described by an on-rate due to crossing of a single free energy barrier, and few experimental works have measured association kinetics under conditions implying force and two-dimensional relative ligand-receptor motion. We use a new laminar flow chamber to measure 2D bond formation with systematic variation of the distribution of encounter durations between antigen and antibody, in a range from 0.1 to 10 ms. Under physiologically relevant forces, 2D association is 100-fold slower than 3D association as studied by surface plasmon resonance assays. Supported by brownian dynamics simulations, our results show that a minimal encounter duration is required for 2D association; an energy landscape featuring a rough initial part might be a reasonable way of accounting for this. By systematically varying the temperature of our experiments, we evaluate roughness at 2kBT, in the range of previously proposed rough parts of landscapes models during dissociation.
authors.affiliation: Laboratoire Adhesion &Inflammation, UMR INSERM 1067, UMR CNRS 7333, Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille, Case 937, 13288 Marseille Cedex 09, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Limozin
authors.affiliation: Laboratoire Adhesion &Inflammation, UMR INSERM 1067, UMR CNRS 7333, Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille, Case 937, 13288 Marseille Cedex 09, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bongrand
authors.affiliation: Laboratoire Adhesion &Inflammation, UMR INSERM 1067, UMR CNRS 7333, Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille, Case 937, 13288 Marseille Cedex 09, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
mesh_terms: D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000378:metabolism*; D000937:Antigen-Antibody Reactions / Q000502:physiology*; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D057446:Hydrodynamics; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008863:Microspheres; D056004:Molecular Dynamics Simulation; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D000936:Antigen-Antibody Complex; D015789:HLA-A2 Antigen; D008024:Ligands; D011947:Receptors, Antigen, B-Cell