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Royal Society of Chemistry, RSC Advances, 110(4), p. 65173-65175, 2014

DOI: 10.1039/c4ra13251c

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Direct observation of ligand-induced receptor dimerization with a bioresponsive hydrogel

Journal article published in 2014 by Jongseong Kim, Yongdoo Park, Ashley C. Brown, L. Andrew Lyon, L. Andrew Lyon ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Multimerization of biomolecules is essential for biological function and thus there is a need for sensitive biochemical assays that determine whether a molecule associates with one or more other molecules in the context of biological function. In this contribution we demonstrate a simple yet versatile method for the identification of physiologically important receptor dimerization events induced by a ligand. Bioresponsive hydrogel microparticles (microgels) conjugated with a receptor, Glycoprotein Ibα (GPIbα), display large changes in optical (microscopic) appearance under conditions known for to promote thrombin-induced GPIbα dimerization. In support of X-ray crystal structures, we identify that one thrombin molecule associates with two GPIbα moieties, which may play a role in efficient hemostatic function by increasing local concentration of GPIbα on platelet surfaces. This microgel assay could provide a new way of studying important physiological and pathological mechanisms related to receptor dimerization and/or clustering.