Journal
ACTA BIOMATERIALIA
Volume 3, Issue 5, Pages 615-629Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2007.03.013
Keywords
biomimetic material; cell culture; ECM; fibroblast; hydrogel; matrix metalloproteinase
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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 alpha(V)beta(3) 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. (c) 2007 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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