Fibroblast traction as a mechanism for collagen morphogenesis

Harris, Albert K.; Stopak, David; Wild, Patricia

doi:10.1038/290249a0

Cited by 795 publications

(528 citation statements)

References 7 publications

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“…However, after a loss of cytoskeletal organization through chemical disruption or through detachment of the gel, which caused cellmediated gel contraction, an upregulation of catabolic gene (MMP-1) expression and inhibition of anabolic gene (α1(I) collagen) expression were observed. The ability of the fibroblasts to remodel their ECM by virtue of an internal contractile mechanism has important implications in wound contracture and connective tissue morphogenesis (Harris et al, 1981;Grinnell, 1994).…”

Section: Regulation Of Gene Expression In Fibroblasts By Mechanical Lmentioning

confidence: 99%

Mechanoregulation of gene expression in fibroblasts

Wang

Thampatty

Lin

et al. 2007

Gene

225

187

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Mechanical loads placed on connective tissues alter gene expression in fibroblasts through mechanotransduction mechanisms by which cells convert mechanical signals into cellular biological events, such as gene expression of extracellular matrix components (e.g., collagen). This mechanical regulation of ECM gene expression affords maintenance of connective tissue homeostasis. However, mechanical loads can also interfere with homeostatic cellular gene expression and consequently cause the pathogenesis of connective tissue diseases such as tendinopathy and osteoarthritis. Therefore, the regulation of gene expression by mechanical loads is closely related to connective tissue physiology and pathology. This article reviews the effects of various mechanical loading conditions on gene regulation in fibroblasts and discusses several mechanotransduction mechanisms. Future research directions in mechanoregulation of gene expression are also suggested.

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Section: Regulation Of Gene Expression In Fibroblasts By Mechanical Lmentioning

confidence: 99%

Mechanoregulation of gene expression in fibroblasts

Wang

Thampatty

Lin

et al. 2007

Gene

225

187

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“…Classically, embryonic induction has been speculated to act very locally (Saxen et al, 1980;Gurdon, 1987). However, spatial information which is required for organization cells and groups of cells during organogenesis has also been suggested to involve long-range communication and also tractional forces have been implicated (Harris et al, 1981;Stopak and Harris, 1982). Tenascin has earlier been shown to be organized along tractional forces between groups of cells in vitro .…”

Section: Discussionmentioning

confidence: 99%

Coordinated induction of cell proliferation and syndecan expression in dental mesenchyme by epithelium: Evidence for diffusible signals

Vainio

1992

Developmental Dynamics

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Epithelial-mesenchymal interactions induce the expression of syndecan, a cell surface proteoglycan, and tenascin, an extracellular matrix glycoprotein in the mesenchymal component of many organ rudiments including the tooth. Experimental recombination cultures of early dental epithelium and mesenchyme were analysed by double immunostaining to compare the distribution of syndecan, tenascin, and proliferating cells (BrdU incorporation) in the induced dental mesenchyme. After 5-9 hr in culture expression of syndecan and tenascin as well as an increase in BrdU incorporation were evident in the mesenchymal cells adjacent to the epithelium and the positive area enlarged with time. Syndecan and tenascin were colocalized only partially in some explants. The expression of syndecan and tenascin in the recombinants correlates with their stage-dependent expression pattern during early tooth development in vivo (Vainio and Thesleff, 1992). The area of increased cell proliferation in the mesenchyme correlated closely with syndecan expression. In none of the explants was increased BrdU incorporation observed in syndecan negative areas. Epithelium induced also condensation of the mesenchymal cells. Induction and spread of the syndecan-positive zone in the dental mesenchyme required close and continuous contact with the epithelium. The mechanism by which the induction of syndecan expression spreads in the mesenchyme was studied in rat-mouse interspecies recombination cultures, using syndecan antibodies that recognize mouse but not rat syndecan. The rat mesenchyme and epithelium were first cultured in contact for 24 hr. Then the epithelium was removed and freshly dissected, "uninduced" mouse mesenchyme was placed in contact with different aspects of the rat mesenchyme. The rat mesenchymal cells that had located next to the epithelial tissue stimulated syndecan expression in adjacent mouse mesenchyme. The induction potential was gradually lost toward the periphery of the rat mesenchyme. Based on these findings we suggest that diffusible signal molecules mediate the spread of syndecan induction in the mesenchyme and that syndecan plays a role in the regulation of cell proliferation.

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“…As cells have previously been shown to interact with their substrate over long distances (10)(11)(12), we tested the effect of cells either sensing or remodeling fibers over variable ranges, from 1 cell radius to 50 cell radii (Fig. 4).…”

Section: Infarct Collagen and Cell Orientations Are Regionally Heteromentioning

confidence: 99%

“…It is possible that this bidirectional interaction (cells determine collagen orientation, which in turn influences cell orientation) can result in a self-reinforcing, positive-feedback loop wherein local pockets of fiber alignment emerge from an initially homogeneous, randomly oriented mixture of fibers. This is especially plausible given the reports that cells can both sense and remodel collagen matrix properties over distances many times their own size (10)(11)(12). Accordingly, to test the hypothesis that heterogeneity in collagen fiber orientation in healing infarct scar can emerge spontaneously from cell-matrix interactions, we employed an agent-based model of infarct scar formation that was previously shown to predict average collagen fiber structure well across multiple experimental models (13).…”

Section: Introductionmentioning

confidence: 99%

Emergence of Collagen Orientation Heterogeneity in Healing Infarcts and an Agent-Based Model

Richardson

Holmes

2016

Biophysical Journal

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Spatial heterogeneity of matrix structure can be an important determinant of tissue function. Although bulk properties of collagen structure in healing myocardial infarcts have been characterized previously, regional heterogeneity in infarct structure has received minimal attention. Herein, we quantified regional variations of collagen and nuclear orientations over the initial weeks of healing after infarction in rats, and employed a computational model of infarct remodeling to test potential explanations for the heterogeneity we observed in vivo. Fiber and cell orientation maps were generated from infarct samples acquired previously at 1, 2, 3, and 6 weeks postinfarction in a rat ligation model. We analyzed heterogeneity by calculating the dot product of each fiber or cell orientation vector with every other fiber or cell orientation vector, and plotting that dot product versus distance between the fibers or cells. This analysis revealed prominent regional heterogeneity, with alignment of both fibers and cell nuclei in local pockets far exceeding the global average. Using an agent-based model of fibroblast-mediated collagen remodeling, we found that similar levels of heterogeneity can spontaneously emerge from initially isotropic matrix via locally reinforcing cell-matrix interactions. Specifically, cells that sensed fiber orientation at a distance or remodeled fibers at a distance by traction-mediated reorientation or aligned deposition gave rise to regionally heterogeneous structures. However, only the simulations in which cells deposited collagen fibers aligned with their own orientation reproduced experimentally measured patterns of heterogeneity across all time points. These predictions warrant experimental follow-up to test the role of such mechanisms in vivo and identify opportunities to control heterogeneity for therapeutic benefit.

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Fibroblast traction as a mechanism for collagen morphogenesis

Cited by 795 publications

References 7 publications

Mechanoregulation of gene expression in fibroblasts

Mechanoregulation of gene expression in fibroblasts

Coordinated induction of cell proliferation and syndecan expression in dental mesenchyme by epithelium: Evidence for diffusible signals

Emergence of Collagen Orientation Heterogeneity in Healing Infarcts and an Agent-Based Model

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