Title: Transient adhesion mediated by ligand-receptor interaction on surfaces of variable nanotopography

Authors: Valentina Lo Schiavo; Philippe Robert; Zohar Mishal; Pierre-Henri Puech; Francesco Gentile; Paolo Decuzzi; Pierre Bongrand; Laurent Limozin

Addresses: Laboratory Adhesion and Inflammation (LAI), INSERM UMR 1067, CNRS UMR 7333, Aix-Marseille University Luminy Campus, Marseille, France ' Laboratory Adhesion and Inflammation (LAI), INSERM UMR 1067, CNRS UMR 7333, Aix-Marseille University Luminy Campus, Marseille, France; Assistance Publique des Hôpitaux de Marseille, Laboratoire d'immunologie, Hôpital de la Conception, 147 Boulevard Baille, 13385 Marseille Cedex 05, France ' Laboratory Adhesion and Inflammation (LAI), INSERM UMR 1067, CNRS UMR 7333, Aix-Marseille University Luminy Campus, Marseille, France ' Laboratory Adhesion and Inflammation (LAI), INSERM UMR 1067, CNRS UMR 7333, Aix-Marseille University Luminy Campus, Marseille, France ' BioNEM Laboratories, University of Catanzaro, Catanzaro, Italy ' Center for the Rational Design of Multifunctional Nanoconstructs, The Methodist Hospital Research Institute, Houston, USA ' Laboratory Adhesion and Inflammation (LAI), INSERM UMR 1067, CNRS UMR 7333, Aix-Marseille University Luminy Campus, Marseille, France; Assistance Publique des Hôpitaux de Marseille, Laboratoire d'immunologie, Hôpital de la Conception, 147 Boulevard Baille, 13385 Marseille Cedex 05, France ' Laboratory Adhesion and Inflammation (LAI), INSERM UMR 1067, CNRS UMR 7333, Aix-Marseille University Luminy Campus, Marseille, France

Abstract: Surface microtopography and nanotopography have been shown to influence cell adhesion and function, including proliferation and differentiation, leading both to fundamental questions and practical applications in the field of biomaterials and nanomedicine. However, the mechanisms of how cells sense topography remain obscure. In this study, we measured directly the effect of nanotopography on the kinetics of association and dissociation of ligand-receptor bonds, which are critically involved in the first steps of cell adhesion. We designed models of biological functionalised surfaces with controlled roughness varying from 2 to 400 nm of root mean square, and controlled ligand density. Tests of transient adhesion of receptor-coated microspheres on these surfaces were performed, using a laminar flow chamber assay. We probed Intercellular Adhesion Molecule ICAM-1-anti-ICAM-1 bond adhesion kinetics in the single molecule limit on smooth and rough substrates. Frequency of adhesion did not exhibit any noticeable dependence on roughness parameter, except at high bead velocity. Detachment rate was also independent of roughness. Finally, leucocyte transient adhesion tests were performed on similar substrates, using variable activating incubating media. Here also, no strong effect of roughness was observed in these conditions. Results are rationalised in terms of the role of local geometry on the access of ligands to receptors.

Keywords: nanotopography; antigen antibodies; molecular environment; leucocyte adhesion; biomaterials; nanomedicine; cell adhesion; biophysics; nanotechnology; ligand-receptor interaction; bond adhesion kinetics; smooth substrates; rough substrates; substrate roughness; detachment rate.

DOI: 10.1504/IJNT.2013.053512

International Journal of Nanotechnology, 2013 Vol.10 No.5/6/7, pp.404 - 418

Published online: 27 Apr 2013 *

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