title: Physically-induced cytoskeleton remodeling of cells in three-dimensional culture.
abstract: Characterizing how cells in three-dimensional (3D) environments or natural tissues respond to biophysical stimuli is a longstanding challenge in biology and tissue engineering. We demonstrate a strategy to monitor morphological and mechanical responses of contractile fibroblasts in a 3D environment. Cells responded to stretch through specific, cell-wide mechanisms involving staged retraction and reinforcement. Retraction responses occurred for all orientations of stress fibers and cellular protrusions relative to the stretch direction, while reinforcement responses, including extension of cellular processes and stress fiber formation, occurred predominantly in the stretch direction. A previously unreported role of F-actin clumps was observed, with clumps possibly acting as F-actin reservoirs for retraction and reinforcement responses during stretch. Responses were consistent with a model of cellular sensitivity to local physical cues. These findings suggest mechanisms for global actin cytoskeleton remodeling in non-muscle cells and provide insight into cellular responses important in pathologies such as fibrosis and hypertension.
authors.affiliation: Department of Mechanical Engineering & Materials Science, Washington University, St. Louis, MO, USA.
authors.forename: Sheng-Lin
authors.initials: SL
authors.lastname: Lee
authors.forename: Ali
authors.initials: A
authors.lastname: Nekouzadeh
authors.forename: Boyd
authors.initials: B
authors.lastname: Butler
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Pryse
authors.forename: William B
authors.initials: WB
authors.lastname: McConnaughey
authors.forename: Adam C
authors.initials: AC
authors.lastname: Nathan
authors.forename: Wesley R
authors.initials: WR
authors.lastname: Legant
authors.forename: Pascal M
authors.initials: PM
authors.lastname: Schaefer
authors.forename: Robert B
authors.initials: RB
authors.lastname: Pless
authors.forename: Elliot L
authors.initials: EL
authors.lastname: Elson
authors.forename: Guy M
authors.initials: GM
authors.lastname: Genin
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002642:Chick Embryo; D003599:Cytoskeleton / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D008962:Models, Theoretical; D022502:Stress Fibers / Q000737:chemistry*; D013314:Stress, Mechanical; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D020741:rho GTP-Binding Proteins; D002118:Calcium