title: Deformation gradients imprint the direction and speed of en masse fibroblast migration for fast healing.
abstract: En masse cell migration is more relevant compared with single-cell migration in physiological processes of tissue formation, such as embryogenesis, morphogenesis, and wound healing. In these situations, cells are influenced by the proximity of other cells including interactions facilitated by substrate mechanics. Here, we found that when fibroblasts migrated en masse over a hydrogel, they established a well-defined deformation field by traction forces and migrated along a trajectory defined by field gradients. The mechanics of the hydrogel determined the magnitude of the gradient. For materials stiff enough to withstand deformation related to cellular traction forces, such patterns did not form. Furthermore, migration patterns functioned poorly on very soft matrices where only a minimal traction gradient could be established. The largest degree of alignment and migration velocity occurred on the gels with the largest gradients. Granulation tissue formation in punch wounds of juvenile pigs was correlated strongly with the modulus of the implanted gel, in agreement with in vitro en masse cell migration studies. These findings provide basic insight into the biomechanical influences on fibroblast movement in early wounds and relevant design criteria for the development of tissue-engineered constructs that aim to stimulate en masse cell recruitment for rapid wound healing.
authors.affiliation: Department of Materials Science and Engineering, SUNY at Stony Brook, Stony Brook, New York, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Department of Biomedical Engineering, SUNY at Stony Brook, Stony Brook, New York, USA.
authors.forename: Kaustabh
authors.initials: K
authors.lastname: Ghosh
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Hung
authors.affiliation: Department of Biomedical Engineering, SUNY at Stony Brook, Stony Brook, New York, USA.
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Macri
authors.affiliation: Jericho Senior High School, Jericho, New York, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Einhorn
authors.affiliation: Department of Materials Science and Engineering, SUNY at Stony Brook, Stony Brook, New York, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Bhatnagar
authors.affiliation: Department of Dermatology, SUNY at Stony Brook, Stony Brook, New York, USA; Department of Oral Biology and Pathology, SUNY at Stony Brook, Stony Brook, New York, USA.
authors.forename: Marcia
authors.initials: M
authors.lastname: Simon
authors.affiliation: Department of Biomedical Engineering, SUNY at Stony Brook, Stony Brook, New York, USA; Department of Dermatology, SUNY at Stony Brook, Stony Brook, New York, USA; Department of Medicine, SUNY at Stony Brook, Stony Brook, New York, USA. Electronic address: richard.clark@stonybrook.edu.
authors.forename: Richard A F
authors.initials: RAF
authors.lastname: Clark
authors.affiliation: Department of Materials Science and Engineering, SUNY at Stony Brook, Stony Brook, New York, USA. Electronic address: miriam.rafailovich@sunysb.edu.
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Rafailovich
mesh_terms: D000328:Adult; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D006097:Granulation Tissue / Q000502:physiology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D061251:Primary Cell Culture; D012685:Sepharose; D023822:Tissue Engineering / Q000379:methods; D014945:Wound Healing / Q000502:physiology*
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D012685:Sepharose