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Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

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TLDR
The important role that matrix stiffness plays in dictating cell behavior during development, tissue homeostasis, and disease progression is reviewed.
Abstract
Tissue development is orchestrated by the coordinated activities of both chemical and physical regulators. While much attention has been given to the role that chemical regulators play in driving development, researchers have recently begun to elucidate the important role that the mechanical properties of the extracellular environment play. For instance, the stiffness of the extracellular environment has a role in orienting cell division, maintaining tissue boundaries, directing cell migration, and driving differentiation. In addition, extracellular matrix stiffness is important for maintaining normal tissue homeostasis, and when matrix mechanics become imbalanced, disease progression may ensue. In this article, we will review the important role that matrix stiffness plays in dictating cell behavior during development, tissue homeostasis, and disease progression.

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Cellular mechanotransduction: From tension to function

TL;DR: A critical review of the recent insights into the molecular basis of cellular mechanotransduction is provided, by analyzing how mechanical stimuli get transformed into a given biological response through the activation of a peculiar genetic program.
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Targeting extracellular matrix stiffness to attenuate disease: From molecular mechanisms to clinical trials

TL;DR: Therapeutic interventions that target tissue stiffening are discussed in the context of their limitations, preclinical drug development efforts, and clinical trials.
References
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Journal ArticleDOI

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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New functions for the matrix metalloproteinases in cancer progression

TL;DR: It is shown that the MMPs have functions other than promotion of invasion, have substrates other than components of the extracellular matrix, and that they function before invasion in the development of cancer.
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TL;DR: It is found that tumors are rigid because they have a stiff stroma and elevated Rho-dependent cytoskeletal tension that drives focal adhesions, disrupts adherens junctions, perturbs tissue polarity, enhances growth, and hinders lumen formation.
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Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling

TL;DR: Reduction of lysyl oxidase-mediated collagen crosslinking prevented MMTV-Neu-induced fibrosis, decreased focal adhesions and PI3K activity, impeded malignancy, and lowered tumor incidence, and data show how collagenCrosslinking can modulate tissue fibrosis and stiffness to force focal adhesion, growth factor signaling and breast malignancies.
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Rho GTPases: Biochemistry and Biology

TL;DR: This review presents the best characterized of these biochemical pathways that control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division.
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