4.5 Article

Shear-driven rolling of DNA-adhesive microspheres

Journal

BIOPHYSICAL JOURNAL
Volume 120, Issue 11, Pages 2102-2111

Publisher

CELL PRESS
DOI: 10.1016/j.bpj.2021.03.038

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Funding

  1. National Science Foundation [CBET-1404826]
  2. National Institutes of Health [R01 HL-103419]

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This study presents an experimental model for simulating cell rolling using polymer microspheres with known adhesive properties. The simulation framework effectively captures the rolling velocity and trajectory variations, confirming its ability to model complex rolling cell systems.
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.

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