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

초록

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 Ib alpha (GPIb alpha), display large changes in optical (microscopic) appearance under conditions known for to promote thrombin-induced GPIb alpha dimerization. In support of X-ray crystal structures, we identify that one thrombin molecule associates with two GPIb alpha moieties, which may play a role in efficient hemostatic function by increasing local concentration of GPIba 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.

키워드