Myofibroblast Development is Characterized by Specific Cell-Cell Adherens Junctions

B. Hinz* ${dagger}$ , P. Pittet*, J. Smith-Clerc*, C. Chaponnier ${ddagger}$ , and J.-J. Meister*

^*Laboratory of Cell Biophysics, Swiss Federal Institute of Technology, 1015 Lausanne, Switzerland; Department of Pathology and Immunology, Centre Medical Universitaire, University of Geneva, 1211 Geneva 4, Switzerland

Monitoring Editor: Paul Matsudaira

Myofibroblasts of wound granulationtissue, in contrast to dermal fibroblasts, join stress fibersat sites of cadherin-type intercellular adherens junctions (AJs).However, the function of myofibroblast AJs, their molecularcomposition and the mechanisms of their formation is largelyunknown. We demonstrate that fibroblasts change cadherin expressionfrom N-cadherin in early wounds to OB-cadherin in contractilewounds, populated with ${alpha}$ -smooth muscle actin ( ${alpha}$ -SMA)-positivemyofibroblasts. A similar shift occurs during myofibroblastdifferentiation in culture and appears to be responsible forthe homotypic segregation of ${alpha}$ -SMA-positive and -negative fibroblastsin suspension. AJs of plated myofibroblasts are reinforced by ${alpha}$ -SMA-mediated contractile activity, resulting in high mechanicalresistance as demonstrated by subjecting cell pairs to hydrodynamicforces in a flow chamber. A peptide that inhibits ${alpha}$ -SMA-mediatedcontractile force causes the reorganization of large stripe-likeAJs to belt-like contacts as shown for EGFP- ${alpha}$ -catenin transfectedcells and is associated with a reduced mechanical resistance.Anti-OB-cadherin but not anti-N-cadherin peptides reduce thecontraction of myofibroblast-populated collagen gels, suggestingthat AJs are instrumental for myofibroblast contractile activity.

Corresponding author. E-mail: boris.hinz{at}epfl.ch