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@ARTICLE{Lembong:835085,
      author       = {Lembong, Josephine and Sabass, Benedikt and Stone, Howard
                      A},
      title        = {{C}alcium oscillations in wounded fibroblast monolayers are
                      spatially regulated through substrate mechanics},
      journal      = {Physical biology},
      volume       = {14},
      number       = {4},
      issn         = {1478-3975},
      address      = {Philadelphia, Pa.},
      publisher    = {IOP Publ.},
      reportid     = {FZJ-2017-04953},
      pages        = {045006 -},
      year         = {2017},
      abstract     = {The maintenance of tissue integrity is essential for the
                      life of multicellular organisms. Healing of a skin wound is
                      a paradigm for how various cell types localize and repair
                      tissue perturbations in an orchestrated fashion. To
                      investigate biophysical mechanisms associated with wound
                      localization, we focus on a model system consisting of a
                      fibroblast monolayer on an elastic substrate. We find that
                      the creation of an edge in the monolayer causes cytosolic
                      calcium oscillations throughout the monolayer. The
                      oscillation frequency increases with cell density, which
                      shows that wound-induced calcium oscillations occur
                      collectively. Inhibition of myosin II reduces the number of
                      oscillating cells, demonstrating a coupling between
                      actomyosin activity and calcium response. The spatial
                      distribution of oscillating cells depends on the stiffness
                      of the substrate. For soft substrates with a Young's modulus
                      E ~ 360 Pa, oscillations occur on average within 0.2 mm
                      distance from the wound edge. Increasing substrate stiffness
                      leads to an average localization of oscillations away from
                      the edge (up to ~0.6 mm). In addition, we use traction
                      force microscopy to determine stresses between cells and
                      substrate. We find that an increase of substrate rigidity
                      leads to a higher traction magnitude. For E  <  ~2
                      kPa, the traction magnitude is strongly concentrated at the
                      monolayer edge, while for E  >  ~8 kPa, traction
                      magnitude is on average almost uniform beneath the
                      monolayer. Thus, the spatial occurrence of calcium
                      oscillations correlates with the cell–substrate traction.
                      Overall, the experiments with fibroblasts demonstrate a
                      collective, chemomechanical localization mechanism at the
                      edge of a wound with a potential physiological role.},
      cin          = {ICS-2},
      ddc          = {530},
      cid          = {I:(DE-Juel1)ICS-2-20110106},
      pnm          = {553 - Physical Basis of Diseases (POF3-553)},
      pid          = {G:(DE-HGF)POF3-553},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000404639300002},
      pubmed       = {pmid:28378710},
      doi          = {10.1088/1478-3975/aa6b67},
      url          = {https://juser.fz-juelich.de/record/835085},
}