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

Abstract

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) actinpromoted intrinsic activation of cadherin extracellular binding. We propose that this plasticity adapts fibroblast adhesions to the changing mechanical microenvironment of tissue under remodeling. Supplementary material available online at

A Molecular Clutch between the Actin Flow and N-Cadherin Adhesions Drives Growth Cone Migration

“…Since those beads coated with a small number of N-cadherin ligands are likely to attach to very few receptors (Thoumine and Meister, 2000), the retrapping events were interpreted as the breaking of a small number of molecular bonds. Because the forces involved are much lower than the 30 -100 pN interaction between individual cadherin molecules (Perret et al, 2004;Pittet et al, 2008), and because beads remain attached to the growth cone surface when the trap is stopped, rupture is unlikely to occur between N-cadherin ligands and receptors. Instead, the 1 pN retrapping events more likely correspond to the rupture of single bonds between the cadherin-catenin complex and actin, which were proposed previously to be highly dynamic .…”

“…9 A, B) or pulled away by centrifuging the cultures upside down (data not shown). We estimate that such protocols produced mechanical forces of ϳ200 -250 pN on the beads (see Materials and Methods), the strength of approximately five cadherin molecular bridges (Perret et al, 2004;Pittet et al, 2008). Therefore, this long-term adhesion assay reflects rather strong contacts involving several N-cadherin molecules.…”

“…Because the optical trap was too weak to restrain microsphere motion, we used larger beads and prevented them from moving rearward by positioning a stiff microneedle downstream , resulting in a continuous slippage of the actin flow beneath the microsphere. The force measured by deflection of the microneedle was ϳ1 nN, i.e., the strength of ϳ10 -20 homophilic bonds between N-cadherins (Perret et al, 2004;Pittet et al, 2008). Thus, slippage in these conditions is likely to involve the complex and random rupture of many receptor-cytoskeleton bonds, impossible to resolve at the individual level as shown in Figure 3.…”

Myofibroblast communication is controlled by intercellular mechanical coupling

“…Myofibroblast differentiation is accompanied by the formation of cell-cell adherens junctions that intercellularly couple contractile stress fibres (Hinz and Gabbiani, 2003a;Hinz et al, 2004;Pittet et al, 2008). In the intracellular portion of adherens junctions, actin filament bundles associate with a protein complex that contains catenins and which mediates binding to the cytoplasmic tail of transmembrane cadherins (Gumbiner, 2005;Nagafuchi, 2001;Weis and Nelson, 2006;Wheelock and Johnson, 2003).…”

Atomic Force Microscopy Imaging of Membrane Proteins

“…These systems allow simultaneous acquisition of the AFM signal and an optical image [21]. These systems promise bright outcomes, being applied in the fields of cancer research [22], cell adhesion [23], actin skeleton structure [24] and protein recognition [21]. In addition, several laboratories are developing high speed AFMs that produce images at "video" speed, higher than 25 frames per second.…”