Molecularly engineered PEG hydrogels

A novel model system for proteolytically mediated cell migration

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

Research output: Contribution to journalArticle

395 Citations (Scopus)

Abstract

Model systems mimicking the extracellular matrix (ECM) have greatly helped in quantifying cell migration in three dimensions and elucidated the molecular determinants of cellular motility in morphogenesis, regeneration, and disease progression. Here we tested the suitability of proteolytically degradable synthetic poly(ethylene glycol) (PEG)-based hydrogels as an ECM model system for cell migration research and compared this designer matrix with the two well-established ECM mimetics fibrin and collagen. Three-dimensional migration of dermal fibroblasts was quantified by time-lapse microscopy and automated single-cell tracking. A broadband matrix metalloproteinase (MMP) inhibitor and tumor necrosis factor-alpha, a potent MMP-inducer in fibroblasts, were used to alter MMP regulation. We demonstrate a high sensitivity of migration in synthetic networks to both MMP modulators: inhibition led to an almost complete suppression of migration in PEG hydrogels, whereas MMP upregulation increased the fraction of migrating cells significantly. Conversely, migration in collagen and fibrin proved to be less sensitive to the above MMP modulators, as their fibrillar architecture allowed for MMP-independent migration through preexisting pores. The possibility of molecularly recapitulating key functions of the natural extracellular microenvironment and the improved protease sensitivity makes PEG hydrogels an interesting model system that allows correlation between protease activity and cell migration.

Original languageEnglish
Pages (from-to)1374-1388
Number of pages15
JournalBiophysical Journal
Volume89
Issue number2
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

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Hydrogels
Matrix Metalloproteinases
Cell Movement
Extracellular Matrix
Fibrin
Peptide Hydrolases
Collagen
Fibroblasts
Cell Tracking
Matrix Metalloproteinase Inhibitors
Ethylene Glycol
Morphogenesis
Disease Progression
Regeneration
Microscopy
Up-Regulation
Tumor Necrosis Factor-alpha
Skin
Research

ASJC Scopus subject areas

  • Biophysics

Cite this

Molecularly engineered PEG hydrogels : A novel model system for proteolytically mediated cell migration. / Raeber, G. P.; Lutolf, M. P.; Hubbell, J. A.

In: Biophysical Journal, Vol. 89, No. 2, 01.08.2005, p. 1374-1388.

Research output: Contribution to journalArticle

Raeber, G. P. ; Lutolf, M. P. ; Hubbell, J. A. / Molecularly engineered PEG hydrogels : A novel model system for proteolytically mediated cell migration. In: Biophysical Journal. 2005 ; Vol. 89, No. 2. pp. 1374-1388.
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