A Hitchhiker's Guide to Mechanobiology

Eyckmans, Jeroen; Boudou, Thomas; Yu, Xiang; Chen, Christopher

doi:10.1016/j.devcel.2011.06.015

Cited by 444 publications

(392 citation statements)

References 163 publications

(179 reference statements)

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“…In the last decade, the expanding research of non-muscle myosin II and mechanobiology in general have highlighted the fact that actomyosin contractility plays a key role in many structural, mechanical and regulatory processes (Eyckmans et al, 2011;Mammoto et al, 2013;Sun and Fu, 2013;Swartz and Lund, 2012). Summarizing the current knowledge in the field brings to light the molecular and functional complexity of actomyosin contractility.…”

Section: Perspectivesmentioning

confidence: 99%

The contractome – a systems view of actomyosin contractility in non-muscle cells

Zaidel-Bar

Guo

Luxenburg

2015

Journal of Cell Science

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Actomyosin contractility is a highly regulated process that affects many fundamental biological processes in each and every cell in our body. In this Cell Science at a Glance article and the accompanying poster, we mined the literature and databases to map the contractome of non-muscle cells. Actomyosin contractility is involved in at least 49 distinct cellular functions that range from providing cell architecture to signal transduction and nuclear activity. Containing over 100 scaffolding and regulatory proteins, the contractome forms a highly complex network with more than 230 direct interactions between its components, 86 of them involving phosphorylation. Mapping these interactions, we identify the key regulatory pathways involved in the assembly of actomyosin structures and in activating myosin to produce contractile forces within non-muscle cells at the exact time and place necessary for cellular function.

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Section: Perspectivesmentioning

confidence: 99%

The contractome – a systems view of actomyosin contractility in non-muscle cells

Zaidel-Bar

Guo

Luxenburg

2015

Journal of Cell Science

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“…Thus, although we refer to the regions that induce tumor cell proliferation and invasion as "high stress," we do so without prejudice. From the perspective of the cell, it is probably more informative to focus on the molecular changes that result from spatial variations in mechanical tone, such as conformational changes in mechanically responsive proteins or activation of mechanically sensitive signaling cascades (26). Some insight into this can be gained from regional analyses of mouse mammary glands, which have found in distal growth regions increased expression of epithelial cell-specific factors that are critical for cancer development, including GATA3 (55) and FGFR2 (56).…”

Section: 29 43 45-48)mentioning

confidence: 99%

“…Normally, cells exert contractile forces against their surrounding microenvironment (26,27). Failure to maintain a balance between these exerted forces and the opposing forces from the microenvironment causes aberrations that promote the progression of disease, including cancer (28).…”

mentioning

confidence: 99%

Host epithelial geometry regulates breast cancer cell invasiveness

Boghaert¹,

Gleghorn²,

Lee

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Breast tumor development is regulated in part by cues from the local microenvironment, including interactions with neighboring nontumor cells as well as the ECM. Studies using homogeneous populations of breast cancer cell lines cultured in 3D ECM have shown that increased ECM stiffness stimulates tumor cell invasion. However, at early stages of breast cancer development, malignant cells are surrounded by normal epithelial cells, which have been shown to exert a tumor-suppressive effect on cocultured cancer cells. Here we explored how the biophysical characteristics of the host microenvironment affect the proliferative and invasive tumor phenotype of the earliest stages of tumor development, by using a 3D microfabrication-based approach to engineer ducts composed of normal mammary epithelial cells that contained a single tumor cell. We found that the phenotype of the tumor cell was dictated by its position in the duct: proliferation and invasion were enhanced at the ends and blocked when the tumor cell was located elsewhere within the tissue. Regions of invasion correlated with high endogenous mechanical stress, as shown by finite element modeling and bead displacement experiments, and modulating the contractility of the host epithelium controlled the subsequent invasion of tumor cells. Combining microcomputed tomographic analysis with finite element modeling suggested that predicted regions of high mechanical stress correspond to regions of tumor formation in vivo. This work suggests that the mechanical tone of nontumorigenic host epithelium directs the phenotype of tumor cells and provides additional insight into the instructive role of the mechanical tumor microenvironment.host-tumor interactions | mechanotransduction | focal adhesion kinase | integrin clustering

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“…Clearly, there are numerous cellular components in addition to focal adhesions, such as cytoskeletal elements, protein trafficking components and ion channels that are involved in mechanical signaling and thus may also contribute to the regulation of durotaxis [13][14][15] . Each of these components could be readily evaluated in our system using similar RNAi approaches.…”

Section: Discussionmentioning

confidence: 99%

A Simplified System for Evaluating Cell Mechanosensing and Durotaxis <em>In Vitro</em>

Goreczny

Wormer

Turner

2015

JoVE

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The composition and mechanical properties of the extracellular matrix are highly variable between tissue types. This connective tissue stroma diversity greatly impacts cell behavior to regulate normal and pathologic processes including cell proliferation, differentiation, adhesion signaling and directional migration. In this regard, the innate ability of certain cell types to migrate towards a stiffer, or less compliant matrix substrate is referred to as durotaxis. This phenomenon plays an important role during embryonic development, wound repair and cancer cell invasion. Here, we describe a straightforward assay to study durotaxis, in vitro, using polydimethylsiloxane (PDMS) substrates. Preparation of the described durotaxis chambers creates a rigidity interface between the relatively soft PDMS gel and a rigid glass coverslip. In the example provided, we have used these durotaxis chambers to demonstrate a role for the cdc42/Rac1 GTPase activating protein, cdGAP, in mechanosensing and durotaxis regulation in human U2OS osteosarcoma cells. This assay is readily adaptable to other cell types and/or knockdown of other proteins of interests to explore their respective roles in mechanosignaling and durotaxis. Video LinkThe video component of this article can be found at

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A Hitchhiker's Guide to Mechanobiology

Cited by 444 publications

References 163 publications

The contractome – a systems view of actomyosin contractility in non-muscle cells

The contractome – a systems view of actomyosin contractility in non-muscle cells

Host epithelial geometry regulates breast cancer cell invasiveness

A Simplified System for Evaluating Cell Mechanosensing and Durotaxis <em>In Vitro</em>

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