title: Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties.
abstract: To successfully induce tissue repair or regeneration in vivo, bioengineered constructs must possess both optimal bioactivity and mechanical strength. This is because cell interaction with the extracellular matrix (ECM) produces two different but concurrent signaling mechanisms: ligation-induced signaling, which depends on ECM biological stimuli, and traction-induced signaling, which depends on ECM mechanical stimuli. In this report, we provide a fundamental understanding of how alterations in mechanical stimuli alone, produced by varying the viscoelastic properties of our bioengineered construct, modulate phenotypic behavior at the whole-cell level. Using a physiologically relevant ECM mimic composed of hyaluronan and fibronectin, we found that adult human dermal fibroblasts modify their mechanical response in order to match substrate stiffness. More specifically, the cells on stiffer substrates had higher modulus and a more stretched and organized actin cytoskeleton (and vice versa), which translated into larger traction forces exerted on the substrate. This modulation of cellular mechanics had contrasting effects on migration and proliferation, where cells migrated faster on softer substrates while proliferating preferentially on the stiffer ones. These findings implicate substrate rigidity as a critical design parameter in the development of bioengineered constructs aimed at eliciting maximal cell and tissue function.
authors.affiliation: Department of Biomedical Engineering, SUNY at Stony Brook, Stony Brook, New York 11794-8165, USA.
authors.forename: Kaustabh
authors.initials: K
authors.lastname: Ghosh
authors.forename: Zhi
authors.initials: Z
authors.lastname: Pan
authors.forename: E
authors.initials: E
authors.lastname: Guan
authors.forename: Shouren
authors.initials: S
authors.lastname: Ge
authors.forename: Yajie
authors.initials: Y
authors.lastname: Liu
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakamura
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Ren
authors.forename: Miriam
authors.initials: M
authors.lastname: Rafailovich
authors.forename: Richard A F
authors.initials: RA
authors.lastname: Clark
mesh_terms: D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000220:Adaptation, Biological; D040761:Biomimetic Materials / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004548:Elasticity; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D018625:Microscopy, Atomic Force; D012867:Skin / Q000166:cytology / Q000378:metabolism; D014783:Viscosity
chemical_list: D000199:Actins