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Natalie A. Dye

Publications and source records attributed to Natalie A. Dye.

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Cell size heterogeneity controls crystallization of the developing fruit fly wing

A fundamental question in biology is to understand how patterns and shapes emerge from the collective interplay of large numbers of cells. Cells forming two-dimensional epithelial tissues behave as active materials that undergo remodeling and spontaneous shape changes. Focusing on the fly wing as a model system, we find that the cellular packing in the wing epithelium transitions from a disordered packing to an ordered, crystalline packing. While previous studies propose a role of tissue shear flow in establishing the ordered cell packing in the fly wing, we reveal a role of cell size heterogeneity. Indeed, we find that even if tissue shear have been inhibited, cell packings in the fruit fly wing epithelium transition from disordered to an ordered packing. We propose that the transition is controlled by the cell size heterogeneity, which is quantified by the cell size polydispersity. To explore the role of cell size polydispersity in controlling cellular packings, we implement polydispersity in a vertex model of epithelial tissues. Through numerical simulations of this model, we show that there is a critical value of cell size polydispersity above which cellular packings are disordered and below which they form a crystalline packing. By analyzing experimental data, we find that cell size polydispersity decreases during fly wing development. The observed dynamics of tissue crystallisation is consistent with the slow ordering kinetics we observe in the vertex model. Therefore, although tissue shear does not control the transition, it significantly enhances the rate of tissue-scale ordering by facilitating alignment of locally ordered crystallites. Our results identify cell size heterogeneity as a control parameter, in both the vertex model and the fruit fly wing epithelium, controlling the transition between ordered and disordered cellular packings.

physics.bio-ph

Cell proliferation maintains cell area polydispersity in the growing fruit fly wing epithelium

Developing epithelial tissues coordinate cell proliferation and mechanical forces to achieve proper size and shape. As epithelial cells tightly adhere together to form the confluent tissue, the distribution of cell areas significantly influences possible patterns of cellular packing and thereby also the mechanics of the epithelium. Therefore, it is important to understand the origin of cell area heterogeneity in developing tissues and, if possible, how to control it. Previous models of cell growth and division have been successful in accounting for experimentally observed area distributions in cultured cells and bacterial colonies, but developing tissues present additional complexity due to self-organized patterns of mechanical stresses that guide morphogenesis. Here, we address this challenge focusing on the D. melanogaster wing disc epithelium. We consider a simple model that couples cell cycle dynamics to tissue mechanics. From time-lapse imaging of the cellular network, we extract all model parameters - cell growth rates, division rates, and mechanical fluctuations - revealing that they all depend on cell size. With these independently measured parameters, our model quantitatively reproduces the observed cell area distribution without any fitting parameters and further predicts tissue pressure gradients, in quantitative agreement with previously published data. Importantly, we find that cell proliferation accounts for 85% of cell area variance, establishing it as the dominant source of packing disorder that influences tissue mechanics and organization.

physics.bio-ph

Cell divisions imprint long lasting elastic strain fields in epithelial tissues

A hallmark of biological tissues, viewed as complex cellular materials, is the active generation of mechanical stresses by cellular processes, such as cell divisions. Each cellular event generates a force dipole that deforms the surrounding tissue. Therefore, a quantitative description of these force dipoles, and their consequences on tissue mechanics, is one of the central problems in understanding the overall tissue mechanics. In this work we analyze previously published experimental data on fruit fly \textit{D. melanogaster} wing epithelia to quantitatively describe the deformation fields induced by a cell-scale force dipole. We find that the measured deformation field can be explained by a simple model of fly epithelium as a linearly elastic sheet. This fact allows us to use measurements of the strain field around cellular events, such as cell divisions, to infer the magnitude and dynamics of the mechanical forces they generate. In particular, we find that cell divisions exert a transient isotropic force dipole field, corresponding to the temporary localisation of the cell nucleus to the tissue surface during the division, and traceless-symmetric force dipole field that remains detectable from the tissue strain field for up to about $3.5$ hours after the division. This is the timescale on which elastic strains are erased by other mechanical processes and therefore it corresponds to the tissue fluidization timescale. In summary, we have developed a method to infer force dipoles induced by cell divisions, by observing the strain field in the surrounding tissues. Using this method we quantitatively characterize mechanical forces generated during a cell division, and their effects on the tissue mechanics.

physics.bio-ph

Inferring the flow properties of epithelial tissues from their geometry

Amorphous materials exhibit complex material proprteties with strongly nonlinear behaviors. Below a yield stress they behave as plastic solids, while they start to yield above a critical stress $Σ_c$. A key quantity controlling plasticity which is, however, hard to measure is the density $P(x)$ of weak spots, where $x$ is the additional stress required for local plastic failure. In the thermodynamic limit $P(x)\sim x^θ$ is singular at $x= 0$ in the solid phase below the yield stress $Σ_c$. This singularity is related to the presence of system spannig avalanches of plastic events. Here we address the question if the density of weak spots and the flow properties of a material can be determined from the geometry of an amporphous structure alone. We show that a vertex model for cell packings in tissues exhibits the phenomenology of plastic amorphous systems. As the yield stress is approached from above, the strain rate vanishes and the avalanches size $S$ and their duration $τ$ diverge. We then show that in general, in materials where the energy functional depend on topology, the value $x$ is proportional to the length $L$ of a bond that vanishes in a plastic event. For this class of models $P(x)$ is therefore readily measurable from geometry alone. Applying this approach to a quantification of the cell packing geometry in the developing wing epithelium of the fruit fly, we find that in this tissue $P(L)$ exhibits a power law with exponents similar to those found numerically for a vertex model in its solid phase. This suggests that this tissue exhibits plasticity and non-linear material properties that emerge from collective cell behaviors and that these material properties govern developmental processes. Our approach based on the relation between topology and energetics suggests a new route to outstanding questions associated with the yielding transition.

physics.bio-ph