title: The mechanical environment modulates intracellular calcium oscillation activities of myofibroblasts.
abstract: Myofibroblast contraction is fundamental in the excessive tissue remodeling that is characteristic of fibrotic tissue contractures. Tissue remodeling during development of fibrosis leads to gradually increasing stiffness of the extracellular matrix. We propose that this increased stiffness positively feeds back on the contractile activities of myofibroblasts. We have previously shown that cycles of contraction directly correlate with periodic intracellular calcium oscillations in cultured myofibroblasts. We analyze cytosolic calcium dynamics using fluorescent calcium indicators to evaluate the possible impact of mechanical stress on myofibroblast contractile activity. To modulate extracellular mechanics, we seeded primary rat subcutaneous myofibroblasts on silicone substrates and into collagen gels of different elastic modulus. We modulated cell stress by cell growth on differently adhesive culture substrates, by restricting cell spreading area on micro-printed adhesive islands, and depolymerizing actin with Cytochalasin D. In general, calcium oscillation frequencies in myofibroblasts increased with increasing mechanical challenge. These results provide new insight on how changing mechanical conditions for myofibroblasts are encoded in calcium oscillations and possibly explain how reparative cells adapt their contractile behavior to the stresses occurring in normal and pathological tissue repair.
authors.affiliation: Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Godbout
authors.forename: Lysianne
authors.initials: L
authors.lastname: Follonier Castella
authors.forename: Eric A
authors.initials: EA
authors.lastname: Smith
authors.forename: Nilesh
authors.initials: N
authors.lastname: Talele
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Chow
authors.forename: Adriano
authors.initials: A
authors.lastname: Garonna
authors.forename: Boris
authors.initials: B
authors.lastname: Hinz
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D001696:Biomechanical Phenomena; D020013:Calcium Signaling; D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism*; D055595:Mechanical Phenomena; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D013314:Stress, Mechanical
chemical_list: D000199:Actins