Single-molecule approach to understanding multivalent binding kinetics

Todd Sulchek, Raymond Friddle, Timothy Ratto, Huguette Albrecht, Sally Denardo, Aleksandr Noy

Research output: Chapter in Book/Report/Conference proceedingChapter

6 Scopus citations

Abstract

Multivalency results from the simultaneous binding of multiple ligands with multiple receptors. Understanding the effect of multivalency on binding kinetics in molecular and cellular systems may aid the development of new types of therapeutics or countermeasures to pathogen infection. Here, we describe a method using single-molecule dynamic force spectroscopy to determine the binding strength of antibody-protein complexes as a function of binding valency in a direct and simple measurement. We used the atomic force microscope to measure the force required to rupture a single complex formed by the MUC1 protein, a cancer indicator, and therapeutic antibodies that target MUC1. We will show that nanomechanical polymer tethers can be used in a new manner to count the number of biological bonds formed. Mechanical work will disrupt these bonds and can be used to quantify the overall kinetics. This ability to form, count, and dissociate biological bonds with nanomechanical forces provides a powerful method to study the physical laws governing the interactions of biological molecules.

Original languageEnglish (US)
Title of host publicationAnnals of the New York Academy of Sciences
Pages74-82
Number of pages9
Volume1161
DOIs
StatePublished - Apr 2009
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1161
ISSN (Print)00778923
ISSN (Electronic)17496632

Keywords

  • Atomic force microscopy
  • Cancer
  • Force spectroscopy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Sulchek, T., Friddle, R., Ratto, T., Albrecht, H., Denardo, S., & Noy, A. (2009). Single-molecule approach to understanding multivalent binding kinetics. In Annals of the New York Academy of Sciences (Vol. 1161, pp. 74-82). (Annals of the New York Academy of Sciences; Vol. 1161). https://doi.org/10.1111/j.1749-6632.2008.04070.x