Mechanisms of 3-D migration and matrix remodeling of fibroblasts within artificial ECMs

G. P. Raeber, M. P. Lutolf, J. A. Hubbell

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

The elucidation of molecular cell-extracellular matrix (ECM) interactions regulating tissue dynamics necessitates straightforward model systems that can dissect the associated physiological complexity into a smaller number of distinct interactions. Here we employ a previously developed artificial ECM model system to study dynamic cell-matrix interactions involved in proteolytic three-dimensional (3-D) migration and matrix remodeling at the level of single cells. Quantitative time-lapse microscopy of primary human fibroblasts exposed to exogenous physiological matrix metalloproteinase (MMP) inhibitors revealed that 3-D migration is dependent on cell seeding density and occurred via highly localized MMP- and tissue inhibitor of metalloproteinases-2-dependent processes. Stimulation of cells by tumor necrosis factor alpha led to a striking augmentation in fibroblast migration that was accompanied by induction of αVβ3 integrin expression. In long-term cultures, extensive localized cellular matrix remodeling resulted in the morphogenesis of single cells into interconnected multicellular networks. Therefore, these tailor-made artificial ECMs can replicate complex 3-D cell-matrix interactions involved in tissue development and regeneration, an important step in the design of next-generation synthetic biomaterials for tissue engineering.

Original languageEnglish (US)
Pages (from-to)615-629
Number of pages15
JournalActa Biomaterialia
Volume3
Issue number5
DOIs
StatePublished - Sep 1 2007

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Keywords

  • Biomimetic material
  • Cell culture
  • ECM
  • Fibroblast
  • Hydrogel
  • Matrix metalloproteinase

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biotechnology
  • Biochemistry
  • Molecular Biology

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