Biophysical regulation of early limb bud morphogenesis

Hopyan, Sevan

doi:10.1016/j.ydbio.2017.06.034

Cited by 11 publications

(11 citation statements)

References 54 publications

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“…This leads to an immediate and testable prediction for experiments on 3D cell aggregates including embryonic zebrafish cells [3] and human breast cancer cells [6], as well as 3D tissue explants from vertebrate embryos [55]. Our model predicts that in the solid s 5.4 » , and s should rise away from that value as tissue fluidizes.…”

Section: Discussionmentioning

confidence: 70%

A geometrically controlled rigidity transition in a model for confluent 3D tissues

2018

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The origin of rigidity in disordered materials is an outstanding open problem in statistical physics. Previously, a class of 2D cellular models has been shown to undergo a rigidity transition controlled by a mechanical parameter that specifies cell shapes. Here, we generalize this model to 3D and find a rigidity transition that is similarly controlled by the preferred surface area S 0 : the model is solid-like below a dimensionless surface area of s S V 5.413 0 0 2 3 º » with V being the average cell volume, and fluid-like above this value. We demonstrate that, unlike jamming in soft spheres, residual stresses are necessary to create rigidity. These stresses occur precisely when cells are unable to obtain their desired geometry, and we conjecture that there is a well-defined minimal surface area possible for disordered cellular structures. We show that the behavior of this minimal surface induces a linear scaling of the shear modulus with the control parameter at the transition point, which is different from the scaling observed in particulate matter. The existence of such a minimal surface may be relevant for biological tissues and foams, and helps explain why cell shapes are a good structural order parameter for rigidity transitions in biological tissues.

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Section: Discussionmentioning

confidence: 70%

A geometrically controlled rigidity transition in a model for confluent 3D tissues

2018

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“…The resurgence of physical approches to morphogenesis 37 has been fueled by progressively sophisticated empirical evaluation of mechanical hypotheses. Numerous contemporary proposals in the field invoke feedback between active cell behaviours and tissue scale properties that underlie tissue shape and organisation [2][3][4]14,22,38,39 . Most of these proposals concern 2D flat or curved tissues for which currently available tools such as microscopic evaluation of cell shape and cytoskeletal organisation, micropipette aspiration, AFM, laser ablation, and ferromagnetic oil droplets have been shown to be sufficient to generate relative or absolute measurements of stiffness, viscosity, cortical tension or stress.…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional tissue stiffness mapping in the mouse embryo supports durotaxis during early limb bud morphogenesis

Zhu

Huang

Samani

et al. 2018

Preprint

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Numerous biophysical hypotheses invoke tissue stiffness as a key parameter for shaping tissue during development and for influencing cell behaviours during disease progression. However, currently available methods are insufficient to test hypotheses that concern the physical properties of bulk tissues. Here we introduce, validate and apply a new 3D magnetic device that generates a uniform magnetic field gradient within a space that is sufficient to accommodate a vertebrate, organ-stage embryo under live conditions. The device allows for rapid, nontoxic measurement of the spatial variation of absolute elastic modulus and viscosity deep within mesenchymal tissues and within epithelia. By applying the device to map the spatiotemporal variation of viscoelastic properties within the early mouse limb bud, we identified an anteriorly biased mesodermal stiffness gradient along which cells move collectively to shape the early bud. Tissue stiffness corresponds to the nascent expression domain of fibronectin that is Wnt5adependent. The findings challenge the notion that Wnt5a regulates cell movements by chemotaxis, and raises the possibility that Wnt5a modifies the tissue microenvironment to promote durotaxis in vivo. Importantly, the ability to precisely measure tissue stiffness in 3D has the potential to instigate and refine mechanisms of development and disease progression. 0

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“…Early limb development represents an accessible model of bulk tissue morphogenesis, and multiple biophysical mechanisms potentially underlie how the limb grows outward from the lateral plate and acquires its particular shape (4). During early budding of the limb, mesodermal cells move collectively into the limb field from the lateral plate in a Wnt5a-dependent manner (5)(6)(7).…”

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confidence: 99%

Spatial mapping of tissue properties in vivo reveals a 3D stiffness gradient in the mouse limb bud

Zhu

Tao

Samani

et al. 2020

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

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Numerous hypotheses invoke tissue stiffness as a key parameter that regulates morphogenesis and disease progression. However, current methods are insufficient to test hypotheses that concern physical properties deep in living tissues. Here we introduce, validate, and apply a magnetic device that generates a uniform magnetic field gradient within a space that is sufficient to accommodate an organ-stage mouse embryo under live conditions. The method allows rapid, nontoxic measurement of the three-dimensional (3D) spatial distribution of viscoelastic properties within mesenchyme and epithelia. Using the device, we identify an anteriorly biased mesodermal stiffness gradient along which cells move to shape the early limb bud. The stiffness gradient corresponds to aWnt5a-dependent domain of fibronectin expression, raising the possibility that durotaxis underlies cell movements. Three-dimensional stiffness mapping enables the generation of hypotheses and potentially the rigorous testing of mechanisms of development and disease.

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Biophysical regulation of early limb bud morphogenesis

Cited by 11 publications

References 54 publications

A geometrically controlled rigidity transition in a model for confluent 3D tissues

A geometrically controlled rigidity transition in a model for confluent 3D tissues

Three-dimensional tissue stiffness mapping in the mouse embryo supports durotaxis during early limb bud morphogenesis

Spatial mapping of tissue properties in vivo reveals a 3D stiffness gradient in the mouse limb bud

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