Cell migration and organization in three-dimensional in vitro culture driven by stiffness gradient

Biotechnol Bioeng. 2016 Nov;113(11):2496-506. doi: 10.1002/bit.26010. Epub 2016 Jun 3.

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.

Keywords: cell mechanics; cell migration; cell movement; cell organization; cell-matrix interactions; cells; stiffness gradient; tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Animals
  • Batch Cell Culture Techniques / methods*
  • Cell Movement / physiology*
  • Cells, Cultured
  • Computer Simulation
  • Elastic Modulus / physiology
  • Female
  • Humans
  • Mechanotransduction, Cellular / physiology*
  • Mice
  • Mice, Inbred C3H
  • Models, Biological*
  • Stress, Mechanical
  • Taxis Response / physiology*
  • Tissue Engineering / methods*