Quantifying cell-generated mechanical forces within living embryonic tissues

Campàs, Otger; Mammoto, Tadanori; Hasso, Sean M.; Sperling, Ralph A.; O’Connell, Daniel J.; Bischof, A.; Maas, Richard L.; Weitz, David A.; Mahadevan, L.; Ingber, Donald E.

doi:10.1038/nmeth.2761

Cited by 357 publications

(352 citation statements)

References 49 publications

Supporting

Mentioning

340

Contrasting

Order By: Relevance

“…Our work also has interesting uses in mechanobiology, as biological tissue is predominantly soft. For example, a recent study embedded droplets in biological tissue and observed their deformations to extract local anisotropic stresses [52]. The coupling between microscopic and macroscopic stress also plays an important role in the tensional homeostasis of soft tissues [53,54].…”

Section: Discussionmentioning

confidence: 99%

Surface tension and the mechanics of liquid inclusions in compliant solids

2015

View full text Add to dashboard Cite

Eshelby's theory of inclusions has wide-reaching implications across the mechanics of materials and structures including the theories of composites, fracture, and plasticity. However, it does not include the effects of surface stress, which has recently been shown to control many processes in soft materials such as gels, elastomers and biological tissue. To extend Eshelby's theory of inclusions to soft materials, we consider liquid inclusions within an isotropic, compressible, linear-elastic solid. We solve for the displacement and stress fields around individual stretched inclusions, accounting for the bulk elasticity of the solid and the surface tension (i.e. isotropic strain-independent surface stress) of the solid-liquid interface. Surface tension significantly alters the inclusion's shape and stiffness as well as its near-and far-field stress fields. These phenomenon depend strongly on the ratio of inclusion radius, R, to an elastocapillary length, L. Surface tension is significant whenever inclusions are smaller than 100L. While Eshelby theory predicts that liquid inclusions generically reduce the stiffness of an elastic solid, our results show that liquid inclusions can actually stiffen a solid when R < 3L/2. Intriguingly, surface tension cloaks the far-field signature of liquid inclusions when R = 3L/2. These results are have far-reaching applications from measuring local stresses in biological tissue, to determining the failure strength of soft composites.

show abstract

Section: Discussionmentioning

confidence: 99%

Surface tension and the mechanics of liquid inclusions in compliant solids

2015

View full text Add to dashboard Cite

show abstract

“…Additional work using sophisticated cogels of Matrigel and other synthetic or naturally derived matrices, with tunable mechanical properties (41), will be necessary to more fully elucidate the mechanoregulatory mechanisms at work during epithelial morphogenesis. Ultimately, these problems will demand interdisciplinary collaborations between engineers, physicists, materials scientists, and cell and developmental biologists and will require new experimental (42) and computational (43) approaches to quantify the mechanical forces and material properties that shape developing tissues.…”

Section: Discussionmentioning

confidence: 99%

Mechanically patterning the embryonic airway epithelium

Varner

Gleghorn

Miller

et al. 2015

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

100

View full text Add to dashboard Cite

Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reactiondiffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo.buckling | instability | mechanical stress | morphodynamics | morphogenesis S pace-filling, branched networks form the basic architecture of several organs, including the lung, kidney, and mammary gland. In the developing embryo, these complex structures originate as simple epithelial tubes. To form a ramified network, the initial tubular geometry is molded by a series of branching events, patterned in both space and time (1-3). In most cases, branching involves reciprocal signaling between adjacent tissues (4, 5), but it remains unclear how the locations of new branches are determined.Airway branching is highly stereotyped in the developing mouse lung (6) and regulated in part by fibroblast growth factors (FGFs) (7). New epithelial branches are thought to emerge at locations adjacent to a prepattern of focal expression of FGF10 in the neighboring mesenchyme (8, 9) (Fig. 1A), a molecular mechanism with remarkable similarity to the induction of Drosophila tracheal branching by the FGF homolog Branchless (10). Moreover, the prepattern of FGF10 is regulated by reciprocal feedback between core signaling pathways, including those downstream of sonic hedgehog, bone morphogenetic protein, Wnt, and Notch (5, 11-13). These molecular signals are thought to interact via a reaction-diffusion mechanism (14, 15) to generate the spatial template of FGF10 (16) and are typically assumed to be sufficient to pattern branch locations along the airway epithelium (5, 10). This rich molecular description, however, overlooks the role that mechanical cues might play in establishing biological patterns. The pattern of villi in the developing gut, for instance, is determined by physical buckling (17,18).When the mesenchyme is removed, thus disrupting reciprocal signaling, isolated epithelia still branch in response to FGF1 or FGF10 (19,20). In these culture models, the exogenous growth factors are present ubiquitously, with no apparent spatial pattern (Fig. 1...

show abstract

“…This could include minor revisions -for example, incorporating stochastic effects can slightly relax the parameter constraint -but could also include major changes, such as implementing a three-component, as opposed a two-component, reaction diffusion model or even considering cellular and mechanical models of patterning. Recent experimental advances suggest that the relevant parameters, such as diffusion constants, molecular degradation rates and tissue material properties, along with sensitivities can be measured, or at least estimated, with reasonable precision in vivo (Akhtar et al, 2011;Campas et al, 2014;Müller et al, 2012). We illustrate this approach by considering the patterning of hair follicles in mammals.…”

Section: Parameter Constraintsmentioning

confidence: 99%

Mathematically guided approaches to distinguish models of periodic patterning

Hiscock

Megason

2015

Development

View full text Add to dashboard Cite

How periodic patterns are generated is an open question. A number of mechanisms have been proposed -most famously, Turing's reactiondiffusion model. However, many theoretical and experimental studies focus on the Turing mechanism while ignoring other possible mechanisms. Here, we use a general model of periodic patterning to show that different types of mechanism (molecular, cellular, mechanical) can generate qualitatively similar final patterns. Observation of final patterns is therefore not sufficient to favour one mechanism over others. However, we propose that a mathematical approach can help to guide the design of experiments that can distinguish between different mechanisms, and illustrate the potential value of this approach with specific biological examples.

show abstract

Quantifying cell-generated mechanical forces within living embryonic tissues

Cited by 357 publications

References 49 publications

Surface tension and the mechanics of liquid inclusions in compliant solids

Surface tension and the mechanics of liquid inclusions in compliant solids

Mechanically patterning the embryonic airway epithelium

Mathematically guided approaches to distinguish models of periodic patterning

Contact Info

Product

Resources

About