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Journal ArticleDOI

Taking Cell-Matrix Adhesions to the Third Dimension

Edna Cukierman, +3 more
- 23 Nov 2001 - 
- Vol. 294, Iss: 5547, pp 1708-1712
TLDR
These distinctive in vivo 3D-matrix adhesions differ in structure, localization, and function from classically described in vitro adhesion, and as such they may be more biologically relevant to living organisms.
Abstract
Adhesions between fibroblastic cells and extracellular matrix have been studied extensively in vitro, but little is known about their in vivo counterparts. Here, we characterized the composition and function of adhesions in three-dimensional (3D) matrices derived from tissues or cell culture. "3D-matrix adhesions" differ from focal and fibrillar adhesions characterized on 2D substrates in their content of alpha5beta1 and alphavbeta3 integrins, paxillin, other cytoskeletal components, and tyrosine phosphorylation of focal adhesion kinase (FAK). Relative to 2D substrates, 3D-matrix interactions also display enhanced cell biological activities and narrowed integrin usage. These distinctive in vivo 3D-matrix adhesions differ in structure, localization, and function from classically described in vitro adhesions, and as such they may be more biologically relevant to living organisms.

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Citations
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Matrix elasticity directs stem cell lineage specification.

TL;DR: Naive mesenchymal stem cells are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types.
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Tissue Cells Feel and Respond to the Stiffness of Their Substrate

TL;DR: An understanding of how tissue cells—including fibroblasts, myocytes, neurons, and other cell types—sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels with which elasticity can be tuned to approximate that of tissues.
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Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering

TL;DR: Although modern synthetic biomaterials represent oversimplified mimics of natural ECMs lacking the essential natural temporal and spatial complexity, a growing symbiosis of materials engineering and cell biology may ultimately result in synthetic materials that contain the necessary signals to recapitulate developmental processes in tissue- and organ-specific differentiation and morphogenesis.
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Myofibroblasts and mechano-regulation of connective tissue remodelling

TL;DR: It is clear that the understanding of the myofibroblast — its origins, functions and molecular regulation — will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.
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Tumour-cell invasion and migration: diversity and escape mechanisms

TL;DR: Cancer cells possess a broad spectrum of migration and invasion mechanisms and learning more about the cellular and molecular basis of these different migration/invasion programmes will help to understand how cancer cells disseminate and lead to new treatment strategies.
References
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Journal ArticleDOI

Focal adhesions, contractility, and signaling

TL;DR: Focal adhesions are sites of tight adhesion to the underlying extracellular matrix developed by cells in culture and are regions of signal transduction that relate to growth control.
Journal ArticleDOI

Integrins: Emerging Paradigms of Signal Transduction

TL;DR: Integrins receive signals from other receptors that lead to activation of ligand binding (inside-out signaling) and matrix assembly and activate intracellular signaling pathways that converse with pathways initiated by soluble ligands to regulate cell functions.
Journal ArticleDOI

Collagen substrata for studies on cell behavior.

TL;DR: The ways in which HCLs can be employed as both two- and three-dimensional substrata in cell behavioral studies are illustrated with some preliminary observations on the form, motility, adhesion, and growth of human diploid cells and two lines of malignant cells.
Journal ArticleDOI

Synergistic Roles for Receptor Occupancy and Aggregation in Integrin Transmembrane Function

TL;DR: Combining antibody-mediated clustering with monovalent ligand occupancy induced accumulation of seven cytoskeletal proteins, thereby mimicking multivalent interactions with fibronectin or polyvalent peptides.
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