New advances in probing cell–extracellular matrix interactions

Liu, Allen; Chaudhuri, Ovijit; Parekh, Sapun H.

doi:10.1039/c6ib00251j

Cited by 65 publications

(45 citation statements)

References 308 publications

(336 reference statements)

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“…[34], so that in the absence of stress (F=0) e ii =P (summation convention applies), and we see that P represents the target area change of a material element. The underlying substrate is assumed to be an elastic material as is the standard for mechanotransduction assays and traction force microscopy [7,9,11]. In this case, the contraction of the cell is resisted by the substrate with the internal cellular stresses determined from the force balance…”

Section: Model Of Differential Contractililty In a Cell On A Deformabmentioning

confidence: 99%

“…Consequently, a range of experimental techniques have been developed to measure cell-derived forces including traction force microscopy and other similar deformation-based approaches [7][8][9]. These, in combination, with substrates of carefully calibrated stiffness enable quantitative investigations into contractility and stiffness sensing [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Differential cellular contractility as a mechanism for stiffness sensing

Dunlop

2019

New J. Phys.

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The ability of cells to sense and respond to the mechanical properties of their environments is fundamental to a range of cellular behaviours, with substrate stiffness increasingly being found to be a key signalling factor. Although active contractility of the cytoskeleton is clearly necessary for stiffness sensing in cells, the physical mechanisms connecting contractility with mechanosensing and molecular conformational change are not well understood. Here we present a contractility-driven mechanism for linking changes in substrate stiffness with internal conformational changes. Cellular contractility is often assumed to imply an associated compressive strain. We show, however, that where the contractility is non-uniform, localized areas of internal stretch can be generated as stiffer substrates are encountered. This suggests a physical mechanism for the stretch-activation of mechanotransductive molecules on stiffer substrates. Importantly, the areas of internal stretch occur deep within the cell and not near the cellular perimeter, which region is more traditionally associated with stiffness sensing through e.g. focal adhesions. This supports recent experimental results on whole-cell mechanically-driven mechanotransduction. Considering cellular shape we show that aspect ratio acts as an additional control parameter, so that the onset of positive strain moves to higher stiffness values in elliptical cells.

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Section: Model Of Differential Contractililty In a Cell On A Deformabmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential cellular contractility as a mechanism for stiffness sensing

Dunlop

2019

New J. Phys.

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“…There is significant evidence that the nanoscale structure of fibronectin in particular plays a key role in regulating diverse cell behaviors [33][34][35] and the same effect is likely to be observed in many other ECM components. Unfortunately, though there are advanced methods to image cell-ECM interaction at the nanoscale using both optical and electron microscopy, it is not yet possible to do so with whole-mount tissues [36]. The cell response to the microenvironment may indeed depend on the nanometer-scale structure of the ECM.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Matrix Structure and Composition in the Early Four-Chambered Embryonic Heart

Jallerat

Feinberg

2020

Cells

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During embryonic development, the heart undergoes complex morphogenesis from a liner tube into the four chambers consisting of ventricles, atria and valves. At the same time, the cardiomyocytes compact into a dense, aligned, and highly vascularized myocardium. The extracellular matrix (ECM) is known to play an important role in this process but understanding of the expression and organization remains incomplete. Here, we performed 3D confocal imaging of ECM in the left ventricle and whole heart of embryonic chick from stages Hamburger-Hamilton 28–35 (days 5–9) as an accessible model of heart formation. First, we observed the formation of a fibronectin-rich, capillary-like networks in the myocardium between day 5 and day 9 of development. Then, we focused on day 5 prior to vascularization to determine the relative expression of fibronectin, laminin, and collagen type IV. Cardiomyocytes were found to uniaxially align prior to vascularization and, while the epicardium contained all ECM components, laminin was reduced, and collagen type IV was largely absent. Quantification of fibronectin revealed highly aligned fibers with a mean diameter of ~500 nm and interfiber spacing of ~3 µm. These structural parameters (volume, spacing, fiber diameter, length, and orientation) provide a quantitative framework to describe the organization of the embryonic ECM.

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“…This awareness has driven a rapid expansion in the development of advanced biophysical techniques that probe the responses of cells to physical cues and to measure cell derived forces, including e.g. traction force microscopy, optical tweezers, molecular force sensors and atomic force microscopy-based approaches [3][4][5][6][7]. In parallel there has been much success in developing engineered tissue scaffolds that can be used in conjunction with cell experiments to control the physical properties of the cellular microenvironment, including substrate stiffness [8,9], topology [9,10] and ligand density and patterning [6,11].…”

Section: Introductionmentioning

confidence: 99%

“…traction force microscopy, optical tweezers, molecular force sensors and atomic force microscopy-based approaches [3][4][5][6][7]. In parallel there has been much success in developing engineered tissue scaffolds that can be used in conjunction with cell experiments to control the physical properties of the cellular microenvironment, including substrate stiffness [8,9], topology [9,10] and ligand density and patterning [6,11]. These advances together have demonstrated that a plethora of individual cellular behaviours respond to physical cues [12][13][14], with gel stiffness identified as a key control parameter.…”

Section: Introductionmentioning

confidence: 99%

Mechanotransduction mechanisms in growing spherically structured tissues

Littlejohns

Dunlop

2018

New J. Phys.

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There is increasing experimental interest in mechanotransduction in multi-cellular tissues as opposed to single cells. This is driven by a growing awareness of the importance of physiologically relevant three-dimensional culture and of cell-cell and cell-gel interactions in directing growth and development. The paradigm biophysical technique for investigating tissue level mechanobiology in this context is to grow model tissues in artificial gels with well-defined mechanical properties. These studies often indicate that the stiffness of the encapsulating gel can significantly alter cellular behaviours. We demonstrate here potential mechanisms linking tissue growth with stiffness-mediated mechanotransduction. We show how tissue growth in gel systems generates points at which there is a significant qualitative change in the cellular stress and strain experienced. We show analytically how these potential switching points depend on the mechanical properties of the constraining gel and predict when they will occur. Significantly, we identify distinct mechanisms that act separately in each of the stress and strain fields at different times. These observations suggest growth as a potential physical mechanism coupling gel stiffness with cellular mechanotransduction in three-dimensional tissues. We additionally show that non-proliferating areas, in the case that the constraining gel is soft compared with the tissue, will expand and contract passively as a result of growth. Central compartment size is thus seen to not be a reliable indicator on its own for growth initiation or active behaviour.

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New advances in probing cell–extracellular matrix interactions

Abstract: This review highlights the application of recent innovations in microtechnologies, biomaterials, and imaging tools for probing cell–ECM interactions.

Cited by 65 publications

References 308 publications

Differential cellular contractility as a mechanism for stiffness sensing

Differential cellular contractility as a mechanism for stiffness sensing

Extracellular Matrix Structure and Composition in the Early Four-Chambered Embryonic Heart

Mechanotransduction mechanisms in growing spherically structured tissues

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