Cancer cell migration within 3D layer-by-layer microfabricated photocrosslinked PEG scaffolds with tunable stiffness

Pranav Soman, Jonathan A. Kelber, Jin Woo Lee, Tracy N. Wright, Kenneth S. Vecchio, Richard L. Klemke, Shaochen Chen

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Our current understanding of 3-dimensional (3D) cell migration is primarily based on results from fibrous scaffolds with randomly organized internal architecture. Manipulations that change the stiffness of these 3D scaffolds often alter other matrix parameters that can modulate cell motility independently or synergistically, making observations less predictive of how cells behave when migrating in 3D. In order to decouple microstructural influences and stiffness effects, we have designed and fabricated 3D polyethylene glycol (PEG) scaffolds that permit orthogonal tuning of both elastic moduli and microstructure. Scaffolds with log-pile architectures were used to compare the 3D migration properties of normal breast epithelial cells (HMLE) and Twist-transformed cells (HMLET). Our results indicate that the nature of cell migration is significantly impacted by the ability of cells to migrate in the third dimension. 2D ECM-coated PEG substrates revealed no statistically significant difference in cell migration between HMLE and HMLET cells among substrates of different stiffness. However, when cells were allowed to move along the third dimension, substantial differences were observed for cell displacement, velocity and path straightness parameters. Furthermore, these differences were sensitive to both substrate stiffness and the presence of the Twist oncogene. Importantly, these 3D modes of migration provide insight into the potential for oncogene-transformed cells to migrate within and colonize tissues of varying stiffness.

Original languageEnglish (US)
Pages (from-to)7064-7070
Number of pages7
JournalBiomaterials
Volume33
Issue number29
DOIs
StatePublished - Oct 2012
Externally publishedYes

    Fingerprint

Keywords

  • Cell migration
  • Mechanical stiffness
  • Microstructure
  • Normal breast epithelial cells
  • Oncogene-transformed cells
  • Scaffold

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this