Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus

Wang, Ning; Tytell, Jessica; Ingber, Donald E.

doi:10.1038/nrm2594

Cited by 1,542 publications

(1,410 citation statements)

References 103 publications

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“…For instance, on the subcellular level, mechanical signals can propagate from the cytoplasm to the nucleus on the order of seconds, resulting in a concomitant mechanochemical conversion 10. However, it is unclear how, and to what extent, these mechanical signals on the small timescales may be integrated to elicit cellular behavior across a broad time spectrum.…”

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confidence: 99%

Adaptable Fast Relaxing Boronate‐Based Hydrogels for Probing Cell–Matrix Interactions

et al. 2018

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Hydrogels with tunable viscoelasticity hold promise as materials that can recapitulate many dynamic mechanical properties found in native tissues. Here, covalent adaptable boronate bonds are exploited to prepare hydrogels that exhibit fast relaxation, with relaxation time constants on the order of seconds or less, but are stable for long‐term cell culture and are cytocompatible for 3D cell encapsulation. Using human mesenchymal stem cells (hMSC) as a model, the fast relaxation matrix mechanics are found to promote cell–matrix interactions, leading to spreading and an increase in nuclear volume, and induce yes‐associated protein/PDZ binding domain nuclear localization at longer times. All of these effects are exclusively based on the hMSCs' ability to physically remodel their surrounding microenvironment. Given the increasingly recognized importance of viscoelasticity in controlling cell function and fate, it is expected that the synthetic strategies and material platform presented should provide a useful system to study mechanotransduction on and within viscoelastic environments and explore many questions related to matrix biology.

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confidence: 99%

Adaptable Fast Relaxing Boronate‐Based Hydrogels for Probing Cell–Matrix Interactions

et al. 2018

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“…Cells are mechanically coupled to the ECM through transmembrane proteins known as integrins 7. These integrins bind specific cell‐adhesive ligands presented by ECM proteins, connecting the ECM to the intracellular actin cytoskeleton.…”

Section: The Stem Cell Micronichementioning

confidence: 99%

Recent Advances in Engineering the Stem Cell Microniche in 3D

Bao¹,

Xie²,

Huck³

2018

Advanced Science

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Conventional 2D cell culture techniques have provided fundamental insights into key biochemical and biophysical mechanisms responsible for various cellular behaviors, such as cell adhesion, spreading, division, proliferation, and differentiation. However, 2D culture in vitro does not fully capture the physical and chemical properties of the native microenvironment. There is a growing body of research that suggests that cells cultured on 2D substrates differ greatly from those grown in vivo. This article focuses on recent progress in using bioinspired 3D matrices that recapitulate as many aspects of the natural extracellular matrix as possible. A range of techniques for the engineering of 3D microenvironment with precisely controlled biophysical and chemical properties, and the impact of these environments on cellular behavior, is reviewed. Finally, an outlook on future challenges for engineering the 3D microenvironment and how such approaches would further our understanding of the influence of the microenvironment on cell function is provided.

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“…Passive mechanical inputs include physical properties such as substrate stiffness, ECM alignment, and adhesive affinity..etc. The static physical property of the microenvironment can have a profound impact on cell physiology, producing active biological outputs in cytoskeleton remodeling, gene expression, changes in membrane trafficking, altered signaling, and stem cell differentiation (4)(5)(6)(7)(8)(9). Active inputs, on the other hand, encompass externally applied forces, such as cell stretching and fluid shear stress.…”

Section: Active Modes Of Mechanotransductionmentioning

confidence: 99%

Biophysical Tools for Cellular and Subcellular Mechanical Actuation of Cell Signaling

Liu

2016

Biophysical Journal

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The ability to spatially control cell signaling can help resolve fundamental biological questions. Optogenetic and chemical dimerization techniques along with fluorescent biosensors to report cell signaling activities have enabled researchers to both visualize and perturb biochemistry in living cells. A number of approaches based on mechanical actuation using forcefield gradients have emerged as complementary technologies to manipulate cell signaling in real time. This review covers several technologies, including optical, magnetic, and acoustic control of cell signaling and behavior and highlights some studies that have led to novel insights. I will also discuss some future direction on repurposing mechanosensitive channel for mechanical actuation of spatial cell signaling.

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Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus

Cited by 1,542 publications

References 103 publications

Adaptable Fast Relaxing Boronate‐Based Hydrogels for Probing Cell–Matrix Interactions

Adaptable Fast Relaxing Boronate‐Based Hydrogels for Probing Cell–Matrix Interactions

Recent Advances in Engineering the Stem Cell Microniche in 3D

Biophysical Tools for Cellular and Subcellular Mechanical Actuation of Cell Signaling

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