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Single‐Molecule Approach to Understanding Multivalent Binding Kinetics
Author(s) -
Sulchek Todd,
Friddle Raymond,
Ratto Timothy,
Albrecht Huguette,
DeNardo Sally,
Noy Aleksandr
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2008.04070.x
Subject(s) - force spectroscopy , kinetics , molecular binding , chemistry , receptor–ligand kinetics , molecule , atomic force microscopy , biophysics , nanotechnology , valency , function (biology) , polymer , chemical physics , receptor , materials science , biochemistry , physics , biology , classical mechanics , organic chemistry , evolutionary biology , linguistics , philosophy
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.