Optically controlled collisions of biological objects to evaluate potent polyvalent inhibitors of virus-cell adhesion

Background: The biochemical and biomechanical determinants of adhesion between two biological objects following a collision are complex, and may vary from one system to another. We wished to develop an assay in which all the relevant factors, including the components of the solution, the relative orientation and the relative collision velocity, are under the user's control. Results: A new assay is described in which two mesoscale particles are caused to collide using two independently controlled optical tweezers (optically controlled collision, OPTCOL), This assay enables precise examination of the probability of adhesion under biologically relevant conditions, The OPTCOL assay was used to evaluate the probability of adhesion of a single erythrocyte to a single virus-coated microsphere, in the absence and presence of a sialic acid-bearing inhibitor, Inhibition constants for the most effective inhibitors could not be measured using other types of assays, The best inhibitor prevented attachment 50 % of the time at a sialic acid concentration of 35 pmol l(-1); it is the most potent known inhibitor of attachment of influenza virus to erythrocytes. Conclusions: OPTCOL is a versatile new bioassay for studying dynamic interactions in biochemistry. It offers an approach to investigating interactions between moving biological objects that is both quantitative and interpretable. The simplicity of the OPTCOL technique suggests broad applicability to the study of adhesion of mesoscale (1-100 mu m) objects in the areas of cell biology, microbiology, medicinal chemistry, and biophysics.