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First published online 26 February 2008
doi: 10.1242/jcs.024877

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Fibrogenic fibroblasts increase intercellular adhesion strength by reinforcing individual OB-cadherin bonds

¹ Laboratory of Cell Biophysics, Institute of Physics of the Complex Matter, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
² Laboratory of Nanostructures and Novel Electronic Materials, Institute of Physics of the Complex Matter, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland

^* Author for correspondence (e-mail: boris.hinz{at}epfl.ch)

Accepted 31 December 2007

We have previously shown that the switch from N-cadherin to OB-cadherin expression increases intercellular adhesion between fibroblasts during their transition from a migratory to a fibrogenic phenotype. Using atomic force microscopy we here show that part of this stronger adhesion is accomplished because OB-cadherin bonds resist twofold higher forces compared with N-cadherin junctions. By assessing the adhesion force between recombinant cadherin dimers and between native cadherins in the membrane of spread fibroblasts, we demonstrate that cadherin bonds are reinforced over time with two distinct force increments. By modulating the degree of lateral cadherin diffusion and F-actin organization we can attribute the resulting three force states to the single-molecule bond rather than to cadherin cluster formation. Notably, association with actin filaments enhances cadherin adhesion strength on the single-molecule level up to threefold; actin depolymerization reduces single-bond strength to the level of cadherin constructs missing the cytoplasmic domain. Hence, fibroblasts reinforce intercellular contacts by: (1) switching from N- to OB-cadherin expression; (2) increasing the strength of single-molecule bonds in three distinct steps; and (3) actin-promoted intrinsic activation of cadherin extracellular binding. We propose that this plasticity adapts fibroblast adhesions to the changing mechanical microenvironment of tissue under remodeling.

Key words: Atomic force microscopy, Myofibroblast, N-cadherin, OB-cadherin, Cytoskeleton

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