title: IgGs are made for walking on bacterial and viral surfaces.
abstract: Binding of antibodies to their cognate antigens is fundamental for adaptive immunity. Molecular engineering of antibodies for therapeutic and diagnostic purposes emerges to be one of the major technologies in combating many human diseases. Despite its importance, a detailed description of the nanomechanical process of antibody-antigen binding and dissociation on the molecular level is lacking. Here we utilize high-speed atomic force microscopy to examine the dynamics of antibody recognition and uncover a principle; antibodies do not remain stationary on surfaces of regularly spaced epitopes; they rather exhibit 'bipedal' stochastic walking. As monovalent Fab fragments do not move, steric strain is identified as the origin of short-lived bivalent binding. Walking antibodies gather in transient clusters that might serve as docking sites for the complement system and/or phagocytes. Our findings could inspire the rational design of antibodies and multivalent receptors to exploit/inhibit steric strain-induced dynamic effects.
authors.affiliation: 1] Center for Advanced Bioanalysis, A-4020 Linz, Austria [2] Institute of Biophysics, Johannes Kepler University Linz, A-4020 Linz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Preiner
authors.affiliation: Bio-AFM Frontier Research Center, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kodera
authors.affiliation: Chang Chun Institute of Applied Chemistry, Chinese Academy Of Sciences, Changchun 5625, China.
authors.forename: Jilin
authors.initials: J
authors.lastname: Tang
authors.affiliation: Institute of Biophysics, Johannes Kepler University Linz, A-4020 Linz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ebner
authors.affiliation: Institute of Applied Physics, Vienna University of Technology, A-1040 Vienna, Austria.
authors.forename: Mario
authors.initials: M
authors.lastname: Brameshuber
authors.affiliation: Max F. Perutz Laboratories, Medical University of Vienna, A-1030 Vienna, Austria.
authors.forename: Dieter
authors.initials: D
authors.lastname: Blaas
authors.affiliation: 1] Department for NanoBiotechnology, University of Natural Resources and Applied Life Sciences Vienna, A-1190 Vienna, Austria [2].
authors.forename: Nicola
authors.initials: N
authors.lastname: Gelbmann
authors.affiliation: Institute of Biophysics, Johannes Kepler University Linz, A-4020 Linz, Austria.
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Gruber
authors.affiliation: 1] Bio-AFM Frontier Research Center, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan [2] Department of Physics, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ando
authors.affiliation: 1] Center for Advanced Bioanalysis, A-4020 Linz, Austria [2] Institute of Biophysics, Johannes Kepler University Linz, A-4020 Linz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Hinterdorfer
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D036022:Capsid Proteins / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D018625:Microscopy, Atomic Force; D011485:Protein Binding / Q000502:physiology; D013269:Stochastic Processes
chemical_list: D000936:Antigen-Antibody Complex; D000942:Antigens, Bacterial; D000956:Antigens, Viral; D001426:Bacterial Proteins; D036022:Capsid Proteins; D000939:Epitopes; D007074:Immunoglobulin G