NDLI: Crosslinking of cell-derived 3D scaffolds up-regulates the stretching and unfolding of new extracellular matrix assembled by reseeded cells

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Crosslinking of cell-derived 3D scaffolds up-regulates the stretching and unfolding of new extracellular matrix assembled by reseeded cells

Content Provider	Royal Society of Chemistry (RSC)
Author	Smith, Michael L. Vogel, Viola Gourdon, Delphine Klotzsch, Enrico Kubow, Kristopher E. Little, William C.
Copyright Year	2009
Abstract	Elevated levels of tissue crosslinking are associated with numerous diseases (cancer stroma, organ fibrosis), and also eliminate the otherwise remarkable clinical successes of tissue-derived scaffolds, instead eliciting a foreign body reaction. Nevertheless, it is not well understood how the initial physical and biochemical properties of cellular microenvironments, stem cell niches, or of 3D tissue scaffolds guide the assembly and remodeling of new extracellular matrix (ECM) that is ultimately sensed by cells. Here, we incorporated FRET-based mechanical strain sensors, either into cell-derived ECM scaffolds or into the fibronectin (Fn) matrix assembled by reseeded fibroblasts, and demonstrated the following. Cell-generated tensile forces change the conformation of Fn in both 3D scaffolds and new matrix over time. The time course by which new matrix fibers are stretched by reseeded cells is accelerated by scaffold crosslinking. Importantly, stretching Fn fibers increases their elastic modulus (rigidity) and alters their biochemical display. Regulated by Fn fiber unfolding, more soluble Fn binds to the native than to the crosslinked scaffolds. Additionally, matrix assembly of fibroblasts is decreased by scaffold crosslinking. Taken together, scaffold crosslinking has a multifactorial impact on the microenvironment that reseeded cells assemble and respond to, with far-reaching implications for tissue engineering and disease physiology.
Starting Page	635
Ending Page	648
Page Count	14
File Format	HTM / HTML PDF
ISSN	17579694
Volume Number	1
Issue Number	11-12
Journal	Integrative Biology
DOI	10.1039/b914996a
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Fn Cancer Stromal cell Fibrosis Stem cell Three-dimensional space Extracellular matrix Fibronectin Conformational change Elastic modulus Tissue engineering Physiology
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Biophysics

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