Computational models for mechanics of morphogenesis

Wyczalkowski, Matthew A.; Chen, Zi; Filas, Benjamen A.; Varner, Victor D.; Taber, Larry A.

doi:10.1002/bdrc.21013

Cited by 90 publications

(74 citation statements)

References 175 publications

(276 reference statements)

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“…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.

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109

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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...

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Section: Discussionmentioning

confidence: 99%

Mechanically patterning the embryonic airway epithelium

Varner

Gleghorn

Miller

et al. 2015

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

Self Cite

109

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“…But researchers are increasingly realizing that many developmental processes can only be studied through multi-scale modeling (Brodland et al, 1994, Davidson 2012Wyczalkowski et al, 2012). In the following we examine in further detail how mechanical force production and propagation of stress and strain contribute to the shaping of the early embryo.…”

Section: Tissue Mechanics In Embryo Developmentmentioning

confidence: 99%

“…In the latter case, individual genes or regulatory circuits can sometimes be 'knocked out' to study their effects, but it is typically not possible to knock out a physical force. However, new experimental techniques afford an examination of physical difference making in biology (Wyczalkowski et al, 2012;Love, forthcoming). Imaging tools such as video or traction force microscopy, confocal time-lapse microscopy, and fluorescent techniques now allow for quantitative measurement of geometry changes and gradient velocities of moving cells (Brodland et al, 2010;Davidson, 2012).…”

Section: The Explanatory Power Of Macroscale Biomechanicsmentioning

confidence: 99%

“…For instance, a portion of the epithelial layer can be cut with a laser to isolate effects of force transformation on other cells from this layer. 19 Additionally, physical models are increasingly supplemented with advanced computer simulations for studying of trajectories of changes in cell and tissue-shapes (Wyczalkowski et al, 2012). Importantly, experimental designs utilizing these new technologies have revealed that treating cell and tissue mechanics as non-explanatory background conditions is misleading because mechanical cues can directly influence cell differentiation and gene expression through force transmission (Hutson & Ma, 2008;Levayer & Lecuit, 2012;Vogel & Sheetz, 2006;Wozniak & Chen, 2009).…”

Section: The Explanatory Power Of Macroscale Biomechanicsmentioning

confidence: 99%

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Biology meets physics: Reductionism and multi-scale modeling of morphogenesis

Green

Batterman

2017

Studies in History and Philosophy of Science Part C: Studies in

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A common reductionist assumption is that macro-scale behaviors can be described "bottom-up" if only sufficient details about lower-scale processes are available. The view that an "ideal" or "fundamental" physics would be sufficient to explain all macro-scale phenomena has been met with criticism from philosophers of biology. Specifically, scholars have pointed to the impossibility of deducing biological explanations from physical ones, and to the irreducible nature of distinctively biological processes such as gene regulation and evolution. This paper takes a step back in asking whether bottom-up modeling is feasible even when modeling simple physical systems across scales. By comparing examples of multi-scale modeling in physics and biology, we argue that the "tyranny of scales" problem presents a challenge to reductive explanations in both physics and biology. The problem refers to the scale-dependency of physical and biological behaviors that forces researchers to combine different models relying on different scale-specific mathematical strategies and boundary conditions. Analyzing the ways in which different models are combined in multi-scale modeling also has implications for the relation between physics and biology. Contrary to the assumption that physical science approaches provide reductive explanations in biology, we exemplify how inputs from physics often reveal the importance of macro-scale models and explanations. We illustrate this through an examination of the role of biomechanics modeling in developmental biology. In such contexts, the relation between models at different scales and from different disciplines is neither reductive nor completely autonomous, but interdependent.

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“…Investigations have shown that tissue-level events, which determine the post-gastrulation body plan by executing a series of millimetersized morphogenetic deformations, are prominent in warmblooded animals. [1][2][3] Here we explore the question-To what extent, if any, are morphogenetic movements spatially regionalized at the tissue level of organization in bird embryos?…”

Section: Introductionmentioning

confidence: 99%

Identification of emergent motion compartments in the amniote embryo

Loganathan¹,

Little²,

Joshi³

et al. 2014

Organogenesis

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The tissue scale deformations (1mm) required to form an amniote embryo are poorly understood. Here, we studied »400 mm-sized explant units from gastrulating quail embryos. The explants deformed in a reproducible manner when grown using a novel vitelline membrane-based culture method. Time-lapse recordings of latent embryonic motion patterns were analyzed after disk-shaped tissue explants were excised from three specific regions near the primitive streak: 1) anterolateral epiblast, 2) posterolateral epiblast, and 3) the avian organizer (Hensen's node). The explants were cultured for 8 hours-an interval equivalent to gastrulation. Both the anterolateral and the posterolateral epiblastic explants engaged in concentric radial/centrifugal tissue expansion. In sharp contrast, Hensen's node explants displayed Cartesian-like, elongated, bipolar deformations-a pattern reminiscent of axis elongation. Time-lapse analysis of explant tissue motion patterns indicated that both cellular motility and extracellular matrix fiber (tissue) remodeling take place during the observed morphogenetic deformations. As expected, treatment of tissue explants with a selective Rho-Kinase (p160ROCK) signaling inhibitor, Y27632, completely arrested all morphogenetic movements. Microsurgical experiments revealed that lateral epiblastic tissue was dispensable for the generation of an elongated midline axisprovided that an intact organizer (node) is present. Our computational analyses suggest the possibility of delineating tissue-scale morphogenetic movements at anatomically discrete locations in the embryo. Further, tissue deformation patterns, as well as the mechanical state of the tissue, require normal actomyosin function. We conclude that amniote embryos contain tissue-scale, regionalized morphogenetic motion generators, which can be assessed using our novel computational time-lapse imaging approach. These data and future studies-using explants excised from overlapping anatomical positions-will contribute to understanding the emergent tissue flow that shapes the amniote embryo.

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Computational models for mechanics of morphogenesis

Cited by 90 publications

References 175 publications

Mechanically patterning the embryonic airway epithelium

Mechanically patterning the embryonic airway epithelium

Biology meets physics: Reductionism and multi-scale modeling of morphogenesis

Identification of emergent motion compartments in the amniote embryo

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