Ligand-receptor binding kinetics in surface plasmon resonance cells: A Monte Carlo analysis

ORAL

Abstract

Surface plasmon resonance (SPR) chips are widely used to measure association and dissociation rates for the binding kinetics between two species of chemicals, e.g., cell receptors and ligands. It is commonly assumed that ligands are spatially well mixed in the SPR region, and thus a mean-field rate equation description is appropriate. This approximation ignores the spatial fluctuations and temporal correlations induced by local rebinding events, which become prominent for slow diffusion rates and high binding rates. We report detailed Monte Carlo simulations of ligand binding kinetics in an SPR cell subject to laminar flow. We extract the binding dynamics by means of the techniques employed in experimental analysis that are motivated by the mean-field approximation. We find major discrepancies in a wide parameter ramge between the thus extracted rates and the known input simulation values. These results underscore the crucial quantitative importance of spatio-temporal correlations in binary reaction kinetics in SPR cell geometries, and demonstrate the failure of a mean-field analysis of SPR cells in the regime of high association rates, where the spatio-temporal correlations due to diffusive transport and ligand-receptor rebinding events dominate the dynamics of SPR systems.

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Authors

  • Jacob Carroll

    Virginia Tech

  • Jonathan Tan

    Duquesne University, Baker Hughes, Hampton University, Korea Research Institute of Standards and Science, Electronics and Telecommunications Research Institute, Texas Christian University, University of North Texas Health Science Center, Austin Peay State University, Virginia Military Institute, Pennsylvania State University, University of Virginia, Washington University, National Institute for Materials Science, Japan, Tokyo Metropolitan University, Japan, Univ of Kentucky, Argonne National Laboratory, Oak Ridge National Laboratory, Univ of Virginia, James Madison University, Department of Chemistry & Biochemistry, High Point University, Department of Chemistry, High Point University, Department of Physics, James Madison University, Department of Physics & Astronomy, Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, VA, Institute of Renewable Energy and Environment Technology, University of Bolton, Bolton, UK, Division of Materials Science and Engineering, Ames Laboratory, US Dept. of Energy, Ames, IA, Lehigh University, University of Pardubice, Universite de Rennes, Jan Dlugosz University, Translume, NSCL/FRIB, Duke University, University of Massachusetts - Amherst, University of St. Andrews, National Radio Astronomy Observatory, University of Florida, Yale University, None, Georgia College & State Univ, Georgia College & State University, National University of Sciences and Technology (NUST), Univ of Tennessee Space Inst, The University of Virginia, Chiang Mai University, DHA Suffa University, Faculty of Chemical Technology, University of Pardubice, Pardubice, Czech Republic, Department of Physics and Astronomy, Austin Peay State University, Clarksville, TN, United States, George Mason University, Northern Virginia Community College, Department of Physics, University of Virginia, Istanbul University, Georgia College and State University, University of Houston, Western Kentucky Univ, James Madison University, Virginia Polytechnic Institute and State University, Pontifica Universidad Catolica de Chile, Trent University, Univ of Arizona, Ohio State University, NRAO, University of Virginia/NRAO

  • Jonathan Tan

    Duquesne University, Baker Hughes, Hampton University, Korea Research Institute of Standards and Science, Electronics and Telecommunications Research Institute, Texas Christian University, University of North Texas Health Science Center, Austin Peay State University, Virginia Military Institute, Pennsylvania State University, University of Virginia, Washington University, National Institute for Materials Science, Japan, Tokyo Metropolitan University, Japan, Univ of Kentucky, Argonne National Laboratory, Oak Ridge National Laboratory, Univ of Virginia, James Madison University, Department of Chemistry & Biochemistry, High Point University, Department of Chemistry, High Point University, Department of Physics, James Madison University, Department of Physics & Astronomy, Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, VA, Institute of Renewable Energy and Environment Technology, University of Bolton, Bolton, UK, Division of Materials Science and Engineering, Ames Laboratory, US Dept. of Energy, Ames, IA, Lehigh University, University of Pardubice, Universite de Rennes, Jan Dlugosz University, Translume, NSCL/FRIB, Duke University, University of Massachusetts - Amherst, University of St. Andrews, National Radio Astronomy Observatory, University of Florida, Yale University, None, Georgia College & State Univ, Georgia College & State University, National University of Sciences and Technology (NUST), Univ of Tennessee Space Inst, The University of Virginia, Chiang Mai University, DHA Suffa University, Faculty of Chemical Technology, University of Pardubice, Pardubice, Czech Republic, Department of Physics and Astronomy, Austin Peay State University, Clarksville, TN, United States, George Mason University, Northern Virginia Community College, Department of Physics, University of Virginia, Istanbul University, Georgia College and State University, University of Houston, Western Kentucky Univ, James Madison University, Virginia Polytechnic Institute and State University, Pontifica Universidad Catolica de Chile, Trent University, Univ of Arizona, Ohio State University, NRAO, University of Virginia/NRAO

  • Uwe C. Tauber

    Department of Physics and Center for Soft Matter and Biological Physics, Virginia Tech, Center for Soft Matter and Biological Physics, Department of Physics, Virginia Tech, Department of Physics and Center for Soft Matter and BIological Physics, Virginia Tech, Virginia Tech, Department of Physics \& CSMBP, Virginia Tech, Blacksburg, Virginia 24061-0435, United States, Virginia Tech University