title: Low-level stretching accelerates cell migration into a gap.
abstract: We observed that radially stretching cell monolayers at a low level (3%) increases the rate at which they migrate to close a gap formed by in vitro injury. Wound healing has been shown to accelerate in vivo when deformations are topically applied, for example, by negative pressure wound therapy. However, the direct effect of deformations on cell migration during gap closure is still unknown. Thus, we have evaluated the effect of radially applied, sustained (static) tensile strain on the kinematics of en mass cell migration. Monolayers of murine fibroblasts were cultured on stretchable, linear-elastic substrates that were subjected to different tensile strains, using a custom-designed three-dimensionally printed stretching apparatus. Immediately following stretching, the monolayer was 'wounded' at its centre, and cell migration during gap closure was monitored and quantitatively evaluated. We observed a significant increase in normalised migration rates and a reduction of gap closure time with 3% stretching, relative to unstretched controls or 6% stretch. Interestingly, the initial gap area was linearly correlated with the maximum migration rate, especially when stretching was applied. Therefore, small deformations applied to cell monolayers during gap closure enhance en mass cell migration associated with wound healing and can be used to fine-tune treatment protocols.
authors.affiliation: Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Samer
authors.initials: S
authors.lastname: Toume
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Amit
authors.identifier: http://orcid.org/0000-0002-0223-7218
authors.initials: A
authors.lastname: Gefen
authors.affiliation: Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Daphne
authors.identifier: http://orcid.org/0000-0002-9670-3418
authors.initials: D
authors.lastname: Weihs
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D051379:Mice; D013718:Tensile Strength / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
keywords: Cell migration; Gap closure; Mechanobiology; Sustained deformations; Wound healing