Relating cell shape and mechanical stress in a spatially disordered epithelium using a vertex-based model

Using a popular vertex-based model to describe a spatially disordered planar epithelial monolayer, we examine the relationship between cell shape and mechanical stress at the cell and tissue level. Deriving expressions for stress tensors starting from an energetic formulation of the model, we show that the principal axes of stress for an individual cell align with the principal axes of shape, and we determine the bulk effective tissue pressure when the monolayer is isotropic at the tissue level. Using simulations for a monolayer that is not under peripheral stress, we fit parameters of the model to experimental data for Xenopus embryonic tissue. The model predicts that mechanical interactions can generate mesoscopic patterns within the monolayer that exhibit long-range correlations in cell shape. The model also suggests that the orientation of mechanical and geometric cues for processes such as cell division are likely to be strongly correlated in real epithelia. Some limitations of the model in capturing geometric features of Xenopus epithelial cells are highlighted.Comment: 29 pages, 10 figures, revisio

Mechanical characterization of disordered and anisotropic cellular monolayers

We consider a cellular monolayer, described using a vertex-based model, for which cells form a spatially disordered array of convex polygons that tile the plane. Equilibrium cell configurations are assumed to minimize a global energy defined in terms of cell areas and perimeters; energy is dissipated via dynamic area and length changes, as well as cell neighbour exchanges. The model captures our observations of an epithelium from a Xenopus embryo showing that uniaxial stretching induces spatial ordering, with cells under net tension (compression) tending to align with (against) the direction of stretch, but with the stress remaining heterogeneous at the single-cell level. We use the vertex model to derive the linearized relation between tissue-level stress, strain and strain-rate about a deformed base state, which can be used to characterize the tissue's anisotropic mechanical properties; expressions for viscoelastic tissue moduli are given as direct sums over cells. When the base state is isotropic, the model predicts that tissue properties can be tuned to a regime with high elastic shear resistance but low resistance to area changes, or vice versa.Comment: 9 figure

Dynamic analysis of actin protrusion assembly and function during Drosophila dorsal closure

The coordinated migration and fusion of epithelial sheets is employed on numerous occasions to shape the developing embryo and to repair tissues as part of the wound healing response. The morphogenetic episode of dorsal closure, whereby a large hole in the dorsal epithelium of the Drosophila embryo is drawn closed, provides a powerful model for the study of such cell movements because of its amenability to live imaging and the outstanding genetic tractability of Drosophila. During dorsal closure, the leading edge epithelial cells surrounding the hole extend dynamic actin protrusions - filopodia and lamellipodia - which reach across the exposed amnioserosa layer and help to zip the epithelial edges together. In this thesis I have employed live imaging to investigate the assembly of these protrusions and to explore their roles during the closure process. I have carried out a detailed live analysis of wild type dorsal closure, which has provided a valuable staging framework with which to compare defective closure in mutant embryos. To begin to understand more about how actin protrusions are assembled by the epithelial leading edge, I have investigated the function of the small GTPase, Rac, by ectopic expression of constitutively active and dominant negative forms of Race1 and also using a triple Rac loss-of-function mutant. The phenotypes I see in Rac mutant cells, where assembly of actin protrusions is either increased or reduced from wild type levels, suggest three roles for the actin protrusions during dorsal closure. Two of these are sensory, enabling leading edge cells to "find" their correct partner on the opposing epithelium, and to "read" contact inhibition cues once the two edges have met. The third is to function in priming cell-cell adhesion events as the two epithelial surfaces fuse. To begin to assess how the filopodia may fulfil these functions I have focused on a subset of unconventional myosins, which in other systems have been found to localise to filopodial tips. I show that one such myosin, Myo10A, localises to the tips of filopodia in cultured Drosophila cells, whilst its knockdown by RNA interference leads to intriguing dorsal closure defects, including segmental mismatching along the midline seam

Force and the spindle: Mechanical cues in mitotic spindle orientation

AbstractThe mechanical environment of a cell has a profound effect on its behaviour, from dictating cell shape to driving the transcription of specific genes. Recent studies have demonstrated that mechanical forces play a key role in orienting the mitotic spindle, and therefore cell division, in both single cells and tissues. Whilst the molecular machinery that mediates the link between external force and the mitotic spindle remains largely unknown, it is becoming increasingly clear that this is a widely used mechanism which could prove vital for coordinating cell division orientation across tissues in a variety of contexts

The impact of mitigation measures on perinatal outcomes during the first nine months of the COVID-19 pandemic: a systematic review with meta-analysis

Acknowledgements Thank you to the authors who provided additional primary data for use in this meta-analysis.Peer reviewedPublisher PD

Decoupling the Roles of Cell Shape and Mechanical Stress in Orienting and Cueing Epithelial Mitosis.

Distinct mechanisms involving cell shape and mechanical force are known to influence the rate and orientation of division in cultured cells. However, uncoupling the impact of shape and force in tissues remains challenging. Combining stretching of Xenopus tissue with mathematical methods of inferring relative mechanical stress, we find separate roles for cell shape and mechanical stress in orienting and cueing division. We demonstrate that division orientation is best predicted by an axis of cell shape defined by the position of tricellular junctions (TCJs), which align with local cell stress rather than tissue-level stress. The alignment of division to cell shape requires functional cadherin and the localization of the spindle orientation protein, LGN, to TCJs but is not sensitive to relative cell stress magnitude. In contrast, proliferation rate is more directly regulated by mechanical stress, being correlated with relative isotropic stress and decoupled from cell shape when myosin II is depleted

Harnessing the NEON data revolution to advance open environmental science with a diverse and data-capable community

It is a critical time to reflect on the National Ecological Observatory Network (NEON) science to date as well as envision what research can be done right now with NEON (and other) data and what training is needed to enable a diverse user community. NEON became fully operational in May 2019 and has pivoted from planning and construction to operation and maintenance. In this overview, the history of and foundational thinking around NEON are discussed. A framework of open science is described with a discussion of how NEON can be situated as part of a larger data constellation—across existing networks and different suites of ecological measurements and sensors. Next, a synthesis of early NEON science, based on >100 existing publications, funded proposal efforts, and emergent science at the very first NEON Science Summit (hosted by Earth Lab at the University of Colorado Boulder in October 2019) is provided. Key questions that the ecology community will address with NEON data in the next 10 yr are outlined, from understanding drivers of biodiversity across spatial and temporal scales to defining complex feedback mechanisms in human–environmental systems. Last, the essential elements needed to engage and support a diverse and inclusive NEON user community are highlighted: training resources and tools that are openly available, funding for broad community engagement initiatives, and a mechanism to share and advertise those opportunities. NEON users require both the skills to work with NEON data and the ecological or environmental science domain knowledge to understand and interpret them. This paper synthesizes early directions in the community’s use of NEON data, and opportunities for the next 10 yr of NEON operations in emergent science themes, open science best practices, education and training, and community building

Morphogenesis: Joining the Dots to Shape an Embryo

In the study of morphogenesis, how upstream signalling events are intricately linked to downstream cytoskeletal organisation is not entirely understood. Recent work in the Drosophila embryo has begun to shed light on this problem