title: Cyclic stress at mHz frequencies aligns fibroblasts in direction of zero strain.
abstract: Recognition of external mechanical signals is vital for mammalian cells. Cyclic stretch, e.g. around blood vessels, is one such signal that induces cell reorientation from parallel to almost perpendicular to the direction of stretch. Here, we present quantitative analyses of both, cell and cytoskeletal reorientation of umbilical cord fibroblasts. Cyclic strain of preset amplitudes was applied at mHz frequencies. Elastomeric chambers were specifically designed and characterized to distinguish between zero strain and minimal stress directions and to allow accurate theoretical modeling. Reorientation was only induced when the applied stretch exceeded a specific amplitude, suggesting a non-linear response. However, on very soft substrates no mechanoresponse occurs even for high strain. For all stretch amplitudes, the angular distributions of reoriented cells are in very good agreement with a theory modeling stretched cells as active force dipoles. Cyclic stretch increases the number of stress fibers and the coupling to adhesions. We show that changes in cell shape follow cytoskeletal reorientation with a significant temporal delay. Our data identify the importance of environmental stiffness for cell reorientation, here in direction of zero strain. These in vitro experiments on cultured cells argue for the necessity of rather stiff environmental conditions to induce cellular reorientation in mammalian tissues.
authors.affiliation: Institute of Complex Systems, ICS-7, Biomechanics, Forschungszentrum Jülich GmbH, Jülich, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Faust
authors.forename: Nico
authors.initials: N
authors.lastname: Hampe
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rubner
authors.forename: Norbert
authors.initials: N
authors.lastname: Kirchgessner
authors.forename: Sam
authors.initials: S
authors.lastname: Safran
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoffmann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Merkel
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D048430:Cell Shape; D004548:Elasticity; D020724:Elastomers; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism; D013314:Stress, Mechanical; D013718:Tensile Strength; D013816:Thermodynamics; D013997:Time Factors; D016596:Vinculin / Q000378:metabolism
chemical_list: D000199:Actins; D020724:Elastomers; D016596:Vinculin; D019000:Phosphotyrosine