Initiation of epithelial wound closure by an active instability at the purse string.

The ability of biological systems to withstand and recover from various disruptions, such as spontaneous genetic mutations and environmental damage, largely relies on intricate feedback mechanisms. We theoretically study the mechanical response of an epithelial tissue facing damage in the form of a circular wound. Our model describes a feedback loop between the generation of active forces in the actomyosin and tissue mechanics, described by the vertex model.

Basolateral Mechanics Prevents Rigidity Transition in Epithelial Monolayers.

The mechanics of epithelial tissues, which is governed by forces generated in various cell regions, is often investigated using two-dimensional models that account for the apically positioned actomyosin structures but neglect basolateral mechanics. We employ a more detailed three-dimensional model to study how lateral surface tensions affect the structure and rigidity of such tissues. We find that cells are apicobasally asymmetric, with one side appearing more ordered than the other depending on target cell apical perimeter.

Graph topological transformations in space-filling cell aggregates.

Cell rearrangements are fundamental mechanisms driving large-scale deformations of living tissues. In three-dimensional (3D) space-filling cell aggregates, cells rearrange through local topological transitions of the network of cell-cell interfaces, which is most conveniently described by the vertex model. Since these transitions are not yet mathematically properly formulated, the 3D vertex model is generally difficult to implement.

A mechanical wave travels along a genetic guide to drive the formation of an epithelial furrow during Drosophila gastrulation.

Epithelial furrowing is a fundamental morphogenetic process during gastrulation, neurulation, and body shaping. A furrow often results from a fold that propagates along a line. How fold formation and propagation are controlled and driven is poorly understood.

Wrinkling Instability in Unsupported Epithelial Sheets.

We investigate the elasticity of an unsupported epithelial monolayer and we discover that unlike a thin solid plate, which wrinkles if geometrically incompatible with the underlying substrate, the epithelium may do so even in the absence of the substrate. From a cell-based model, we derive an exact elasticity theory and discover wrinkling driven by the differential apico-basal surface tension. Our theory is mapped onto that for supported plates by introducing a phantom substrate whose stiffness is finite beyond a critical differential tension.

Active Instability and Nonlinear Dynamics of Cell-Cell Junctions.

Active cell-junction remodeling is important for tissue morphogenesis, yet its underlying physics is not understood. We study a mechanical model that describes junctions as dynamic active force dipoles. Their instability can trigger cell intercalations by a critical collapse.

Morphologies of compressed active epithelial monolayers.

Using a three-dimensional active vertex model, we numerically study the shapes of strained unsupported epithelial monolayers subject to active junctional noise due to stochastic binding and unbinding of myosin. We find that while uniaxial, biaxial, and isotropic in-plane compressive strains do lead to the formation of longitudinal, herringbone pattern, and labyrinthine folds, respectively, the villus morphology characteristic of, e.g.

Elasticity, Stability, and Quasioscillations of Cell-Cell Junctions in Solid Confluent Epithelia.

Macroscopic properties and shapes of biological tissues depend on the remodeling of cell-cell junctions at the microscopic scale. We propose a theoretical framework that couples a vertex model of solid confluent tissues with the dynamics describing generation of local force dipoles in the junctional actomyosin. Depending on the myosin turnover rate, junctions either preserve stable length or collapse to initiate cell rearrangements.

Publisher Correction: Mechanics of a multilayer epithelium instruct tumour architecture and function.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Collective cell mechanics of epithelial shells with organoid-like morphologies.

The study of organoids, artificially grown cell aggregates with the functionality and small-scale anatomy of real organs, is one of the most active areas of research in biology and biophysics, yet the basic physical origins of their different morphologies remain poorly understood. Here, we propose a mechanistic theory of epithelial shells which resemble small-organoid morphologies. Using a 3D surface tension-based vertex model, we reproduce the characteristic shapes from branched and budded to invaginated structures.

Solid-fluid transition and cell sorting in epithelia with junctional tension fluctuations.

Tissues transition between solid-like and fluid-like behavior, which has major implications for morphogenesis and disease. These transitions can occur due to changes in the intrinsic shape of constituent cells and cell motility. We consider an alternative mechanism by studying tissues that explore the energy landscape through stochastic dynamics, driven by turnover of junctional molecular motors.

Cell-Size Pleomorphism Drives Aberrant Clone Dispersal in Proliferating Epithelia.

As epithelial tissues develop, groups of cells related by descent tend to associate in clonal populations rather than dispersing within the cell layer. While this is frequently assumed to be a result of differential adhesion, precise mechanisms controlling clonal cohesiveness remain unknown. Here we employ computational simulations to modulate epithelial cell size in silico and show that junctions between small cells frequently collapse, resulting in clone-cell dispersal among larger neighbors.

Nuclear (Bio)physics in the Embryo.

Deneke et al. (2019) discover that dynamic interactions of cell cycle and actomyosin contractility systems synchronize nuclear cleavages, generating a cytoplasmic flow that results in a spatially uniform distribution of zygotic nuclei in the early Drosophila embryo. This work underscores the importance of self-organizing mechanisms before the onset of zygotic transcription.

Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription.

The thirteen nuclear cleavages that give rise to the Drosophila blastoderm are some of the fastest known cell cycles [1]. Surprisingly, the fertilized egg is provided with at most one-third of the dNTPs needed to complete the thirteen rounds of DNA replication [2]. The rest must be synthesized by the embryo, concurrent with cleavage divisions.

Syncytial germline architecture is actively maintained by contraction of an internal actomyosin corset.

Syncytial architecture is an evolutionarily-conserved feature of the germline of many species and plays a crucial role in their fertility. However, the mechanism supporting syncytial organization is largely unknown. Here, we identify a corset-like actomyosin structure within the syncytial germline of Caenorhabditis elegans, surrounding the common rachis.

Fluidization of epithelial sheets by active cell rearrangements.

We theoretically explore fluidization of epithelial tissues by active T1 neighbor exchanges. We show that the geometry of cell-cell junctions encodes important information about the local features of the energy landscape, which we support by an elastic theory of T1 transformations. Using a 3D vertex model, we show that the degree of active noise driving forced cell rearrangements governs the stress-relaxation timescale of the tissue.

Quantitative Morphology of Epithelial Folds.

The shape of spatially modulated epithelial morphologies such as villi and crypts is usually associated with the epithelium-stroma area mismatch leading to buckling. We propose an alternative mechanical model based on intraepithelial stresses generated by differential tensions of apical, lateral, and basal sides of cells as well as on the elasticity of the basement membrane. We use it to theoretically study longitudinal folds in simple epithelia and we identify four types of corrugated morphologies: compact, invaginated, evaginated, and wavy.

Theory of epithelial elasticity.

We propose an elastic theory of epithelial monolayers based on a two-dimensional discrete model of dropletlike cells characterized by differential surface tensions of their apical, basal, and lateral sides. We show that the effective tissue bending modulus depends on the apicobasal differential tension and changes sign at the transition from the flat to the fold morphology. We discuss three mechanisms that stabilize the finite-wavelength fold structures: Physical constraint on cell geometry, hard-core interaction between non-neighboring cells, and bending elasticity of the basement membrane.

Embryo-scale tissue mechanics during Drosophila gastrulation movements.

Morphogenesis of an organism requires the development of its parts to be coordinated in time and space. While past studies concentrated on defined cell populations, a synthetic view of the coordination of these events in a whole organism is needed for a full understanding. Drosophila gastrulation begins with the embryo forming a ventral furrow, which is eventually internalized.