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About the Level of Stress Between Myofibroblasts
Author(s) -
Pittet P,
Meister JJ,
Hinz B
Publication year - 2005
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.130117u.x
Subject(s) - myofibroblast , fibroblast , adherens junction , cadherin , microbiology and biotechnology , chemistry , actin , adhesion , wound healing , stress fiber , cell adhesion , focal adhesion , biophysics , cell , pathology , biology , immunology , in vitro , fibrosis , biochemistry , medicine , organic chemistry
Fibroblast to myofibroblast modulation is characterized by expression of α‐smooth muscle actin (α‐SMA) and represents a crucial step in granulation tissue contraction during wound healing. We have recently demonstrated that myofibroblasts develop cadherin‐type cell‐cell adherens junctions (AJs), which join stress fibers over the cell membrane. Cadherin expression changes from N‐cadherin to OB‐cadherin upon TGF‐β induced myofibroblast differentiation in culture and coincides with the enlargement of AJs. We here show that myofibroblast AJs exhibit a higher mechanical resistance compared with that of α‐SMA‐negative fibroblasts by measuring the binding strength between two cells. (1) By separating two suspended cells placed in contact with laser tweezers, we revealed two types of Ca 2+ ‐dependent adhesion bonds with different strength. The first bond exhibited a breaking force of 5.5 ± 1.5 nN and existed in both, fibroblasts and myofibroblasts. The strength of the second bond differed between the two cells, breaking at 18.2 ± 0.8 nN in fibroblasts and at 23.0 ± 1.5 nN in myofibroblasts. Measuring the adhesion force between two plated cells by atomic force microscopy after short contact grossly confirmed these observations. Since no cyoskeletal reinforcement was involved in these experimental conditions, we suggest that these differences represent the different cadherins involved in (myo)fibroblast adhesion. (2) Subjecting suspended cells that were attached to plated cells to hydrodynamic forces in a flow chamber demonstrated ∼18% higher adhesion of myofibroblasts over fibroblasts at shear forces of 4 Nm −2 . This higher adhesion was reduced to the level of fibroblast attachment by a peptide that inhibits α‐SMA‐mediated contraction, indicating AJ reinforcement by α‐SMA‐positive stress fibers. To conclude, high cell‐cell adhesion of myofibroblasts appears to be determined by their specific cadherin pattern and by α‐SMA‐mediated mechanical reinforcement of AJs.