151. A Rough Energy Landscape to Describe Surface-Linked Antibody and Antigen Bond Formation.
- Author
-
Limozin L, Bongrand P, and Robert P
- Subjects
- HLA-A2 Antigen chemistry, HLA-A2 Antigen metabolism, Humans, Hydrodynamics, In Vitro Techniques, Kinetics, Ligands, Microspheres, Molecular Dynamics Simulation, Receptors, Antigen, B-Cell chemistry, Receptors, Antigen, B-Cell metabolism, Surface Plasmon Resonance, Antigen-Antibody Complex chemistry, Antigen-Antibody Complex metabolism, Antigen-Antibody Reactions physiology
- 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 2k
B T, in the range of previously proposed rough parts of landscapes models during dissociation.- Published
- 2016
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