title: Tensional homeostasis in single fibroblasts.
abstract: Adherent cells generate forces through acto-myosin contraction to move, change shape, and sense the mechanical properties of their environment. They are thought to maintain defined levels of tension with their surroundings despite mechanical perturbations that could change tension, a concept known as tensional homeostasis. Misregulation of tensional homeostasis has been proposed to drive disorganization of tissues and promote progression of diseases such as cancer. However, whether tensional homeostasis operates at the single cell level is unclear. Here, we directly test the ability of single fibroblast cells to regulate tension when subjected to mechanical displacements in the absence of changes to spread area or substrate elasticity. We use a feedback-controlled atomic force microscope to measure and modulate forces and displacements of individual contracting cells as they spread on a fibronectin-patterned atomic-force microscope cantilever and coverslip. We find that the cells reach a steady-state contraction force and height that is insensitive to stiffness changes as they fill the micropatterned areas. Rather than maintaining a constant tension, the fibroblasts altered their contraction force in response to mechanical displacement in a strain-rate-dependent manner, leading to a new and stable steady-state force and height. This response is influenced by overexpression of the actin crosslinker α-actinin, and rheology measurements reveal that changes in cell elasticity are also strain- rate-dependent. Our finding of tensional buffering, rather than homeostasis, allows cells to transition between different tensional states depending on how they are displaced, permitting distinct responses to slow deformations during tissue growth and rapid deformations associated with injury.
authors.affiliation: Biophysics Graduate Group, University of California, Berkeley, California; Department of Bioengineering, University of California, Berkeley, California.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Webster
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California; University of California Berkeley/University of California San Francisco Graduate Group in Bioengineering, Berkeley, California.
authors.forename: Win Pin
authors.initials: WP
authors.lastname: Ng
authors.affiliation: Biophysics Graduate Group, University of California, Berkeley, California; Department of Bioengineering, University of California, Berkeley, California; University of California Berkeley/University of California San Francisco Graduate Group in Bioengineering, Berkeley, California; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California. Electronic address: fletch@berkeley.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Fletcher
mesh_terms: D000185:Actinin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004548:Elasticity; D005347:Fibroblasts / Q000737:chemistry* / Q000378:metabolism; D006706:Homeostasis; D051379:Mice; D041681:NIH 3T3 Cells; D013718:Tensile Strength
chemical_list: D000185:Actinin