title: The direction of stretch-induced cell and stress fiber orientation depends on collagen matrix stress.
abstract: Cell structure depends on both matrix strain and stiffness, but their interactive effects are poorly understood. We investigated the interactive roles of matrix properties and stretching patterns on cell structure by uniaxially stretching U2OS cells expressing GFP-actin on silicone rubber sheets supporting either a surface-adsorbed coating or thick hydrogel of type-I collagen. Cells and their actin stress fibers oriented perpendicular to the direction of cyclic stretch on collagen-coated sheets, but oriented parallel to the stretch direction on collagen gels. There was significant alignment parallel to the direction of a steady increase in stretch for cells on collagen gels, while cells on collagen-coated sheets did not align in any direction. The extent of alignment was dependent on both strain rate and duration. Stretch-induced alignment on collagen gels was blocked by the myosin light-chain kinase inhibitor ML7, but not by the Rho-kinase inhibitor Y27632. We propose that active orientation of the actin cytoskeleton perpendicular and parallel to direction of stretch on stiff and soft substrates, respectively, are responses that tend to maintain intracellular tension at an optimal level. Further, our results indicate that cells can align along directions of matrix stress without collagen fibril alignment, indicating that matrix stress can directly regulate cell morphology.
authors.affiliation: Department of Biomedical Engineering, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Tondon
authors.affiliation: Department of Biomedical Engineering, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Roland
authors.initials: R
authors.lastname: Kaunas
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism*; D010766:Phosphorylation; D022502:Stress Fibers / Q000502:physiology*; D013314:Stress, Mechanical; D014407:Tumor Cells, Cultured; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D003094:Collagen; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase