title: Cell migration and organization in three-dimensional in vitro culture driven by stiffness gradient.
abstract: Durotaxis, a phenomenon that cells move according to changes in stiffness of the extra cellular matrix, has emerged as a crucial parameter controlling cell migration behavior. The current study provides a simple method to generate three-dimensional continuous stiffness variations without changing other physical characteristics of the extra cellular environment. Using Finite Element simulations, the stiffness and the stiffness gradient variations are evaluated quantitatively, leading to an analysis of the dependence of cell migration behavior on the substrate stiffness parameters. We tested various cell lines on several 3-D environments. The durotaxis results show that the cell migration velocity does not have any consistency with the stiffness of the substrate, rather it is more related to the stiffness gradient of the substrate. This finding suggests a new mechanism underlying the durotaxis phenomenon, highlighting the importance of the substrate stiffness gradient, rather than the stiffness itself. Biotechnol. Bioeng. 2016;113: 2496-2506. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Danielle
authors.initials: D
authors.lastname: Joaquin
authors.affiliation: Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Michael
authors.initials: M
authors.lastname: Grigola
authors.affiliation: Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213.
authors.forename: Gubeum
authors.initials: G
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Engineering, University of Missouri-Columbia, Columbia, Missouri.
authors.forename: Christopher
authors.initials: C
authors.lastname: Blasius
authors.affiliation: Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Daniel
authors.initials: D
authors.lastname: Perlitz
authors.affiliation: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Ziegler
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Ann
authors.initials: A
authors.lastname: Nardulli
authors.affiliation: Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213. kjhsia@cmu.edu.|Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213. kjhsia@cmu.edu.
authors.forename: K Jimmy
authors.initials: KJ
authors.lastname: Hsia
mesh_terms: D000328:Adult; D000818:Animals; D061249:Batch Cell Culture Techniques / Q000379:methods*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D055119:Elastic Modulus / Q000502:physiology; D005260:Female; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008954:Models, Biological; D013314:Stress, Mechanical; D000071442:Taxis Response / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*
keywords: cell mechanics; cell migration; cell movement; cell organization; cell-matrix interactions; cells; stiffness gradient; tissue engineering