Shear-driven rolling of DNA-adhesive microspheres

• Published in: Biophysical journal 2021-06, Vol.120 (11), p.2102-2111
• Main Authors: Porter, Christopher L., Diamond, Scott L., Sinno, Talid, Crocker, John C.
• Format: Article
• Language: English
• Subjects: Adhesives; Cell Adhesion; DNA; Leukocyte Rolling; Leukocytes; Microspheres
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/j.bpj.2021.03.038

Many biologically important cell binding processes, such as the rolling of leukocytes in the vasculature, are multivalent, being mediated by large numbers of weak binding ligands. Quantitative agreement between experiments and models of rolling has been elusive and often limited by the poor understanding of the binding and unbinding kinetics of the ligands involved. Here, we present a cell-free experimental model for such rolling, consisting of polymer microspheres whose adhesion to a glass surface is mediated by ligands with well-understood force-dependent binding free energy—short complementary DNA strands. We observe robust rolling activity for certain values of the shear rate and the grafted DNA strands’ binding free energy and force sensitivity. The simulation framework developed to model leukocyte rolling, adhesive dynamics, quantitatively captures the mean rolling velocity and lateral diffusivity of the experimental particles using known values of the experimental parameters. Moreover, our model captures the velocity variations seen within the trajectories of single particles. Particle-to-particle variations can be attributed to small, plausible differences in particle characteristics. Overall, our findings confirm that state-of-the-art adhesive dynamics simulations are able to capture the complex physics of particle rolling, boding well for their extension to modeling more complex systems of rolling cells.