The mechanics of cephalic furrow formation in the Drosophila embryo.

Cephalic furrow formation (CFF) is a major morphogenetic movement during gastrulation in Drosophila melanogaster embryos that gives rise to a deep, transitory epithelial invagination. Recent studies have identified the individual cell shape changes that drive the initiation and progression phases of CFF; however, the underlying mechanics are not yet well understood. During the progression phase, the furrow deepens as columnar cells from both the anterior and posterior directions fold inwards rotating by 90°. To analyze the mechanics of this process, we have developed an advanced two-dimensional lateral vertex model that includes multinode representation of cellular membranes and allows us to capture the membrane curvature associated with pressure variation. Our investigations reveal some key potential mechanical features of CFF, as follows. When cells begin to roll over the cephalic furrow cleft, they become wedge shaped as their apical cortices and overlying membranes expand, lateral cortices and overlying membranes release tension, internal pressures drop, and basal cortices and membranes contract. Then, cells reverse this process by shortening apical cortices and membranes, increasing lateral tension, and causing internal pressures to rise. Since the basal membranes expand, the cells recover their rotated columnar shape once in the furrow. Interestingly, our findings indicate that the basal membranes may be passively reactive throughout the progression phase. We also find that the smooth rolling of cells over the cephalic furrow cleft necessitates that internalized cells provide a solid base through high levels of membrane tension and internal pressure, which allows the transmission of tensile force that pulls new cells into the furrow. These results lead us to suggest that CFF helps to establish a baseline tension across the apical surface of the embryo to facilitate cellular coordination of other morphogenetic movements via mechanical stress feedback mechanisms.

Enhanced flow rate by the concentration mechanism of Tetris particles when discharged from a hopper with an obstacle.

We apply a holistic two-dimensional (2D) Tetris-like model, where particles move based on prescribed rules, to investigate the flow rate enhancement from a hopper. This phenomenon was originally reported in the literature as a feature of placing an obstacle at an optimal location near the exit of a hopper discharging athermal granular particles under gravity. We find that this phenomenon is limited to a system of sufficiently many particles. In addition to the waiting room effect, another mechanism able to explain and create the flow rate enhancement is the concentration mechanism of particles on their way to reaching the hopper exit after passing the obstacle. We elucidate the concentration mechanism by decomposing the flow rate into its constituent variables: the local area packing fraction ϕ_{l}^{E} and the averaged particle velocity v_{y}^{E} at the hopper exit. In comparison to the case without an obstacle, our results show that an optimally placed obstacle can create a net flow rate enhancement of relatively weakly driven particles, caused by the exit-bottleneck coupling if ϕ_{l}^{E}>ϕ_{o}^{c}, where ϕ_{o}^{c} is a characteristic area packing fraction marking a transition from fast to slow flow regimes of Tetris particles. Utilizing the concentration mechanism by artificially guiding particles into the central sparse space under the obstacle or narrowing the hopper exit angle under the obstacle, we can create a manmade flow rate peak of relatively strongly driven particles that initially exhibit no flow rate peak. Additionally, the enhanced flow rate can be maximized by an optimal obstacle shape, particle acceleration rate toward the hopper exit, or exit geometry of the hopper.

Mechanical feedback and robustness of apical constrictions in Drosophila embryo ventral furrow formation.

Formation of the ventral furrow in the Drosophila embryo relies on the apical constriction of cells in the ventral region to produce bending forces that drive tissue invagination. In our recent paper we observed that apical constrictions during the initial phase of ventral furrow formation produce elongated patterns of cellular constriction chains prior to invagination and argued that these are indicative of tensile stress feedback. Here, we quantitatively analyze the constriction patterns preceding ventral furrow formation and find that they are consistent with the predictions of our active-granular-fluid model of a monolayer of mechanically coupled stress-sensitive constricting particles. Our model shows that tensile feedback causes constriction chains to develop along underlying precursor tensile stress chains that gradually strengthen with subsequent cellular constrictions. As seen in both our model and available optogenetic experiments, this mechanism allows constriction chains to penetrate or circumvent zones of reduced cell contractility, thus increasing the robustness of ventral furrow formation to spatial variation of cell contractility by rescuing cellular constrictions in the disrupted regions.

Embryo as an active granular fluid: stress-coordinated cellular constriction chains.

Mechanical stress plays an intricate role in gene expression in individual cells and sculpting of developing tissues. However, systematic methods of studying how mechanical stress and feedback help to harmonize cellular activities within a tissue have yet to be developed. Motivated by our observation of the cellular constriction chains (CCCs) during the initial phase of ventral furrow formation in the Drosophila melanogaster embryo, we propose an active granular fluid (AGF) model that provides valuable insights into cellular coordination in the apical constriction process. In our model, cells are treated as circular particles connected by a predefined force network, and they undergo a random constriction process in which the particle constriction probability P is a function of the stress exerted on the particle by its neighbors. We find that when P favors tensile stress, constricted particles tend to form chain-like structures. In contrast, constricted particles tend to form compact clusters when P favors compression. A remarkable similarity of constricted-particle chains and CCCs observed in vivo provides indirect evidence that tensile-stress feedback coordinates the apical constriction activity. Our particle-based AGF model will be useful in analyzing mechanical feedback effects in a wide variety of morphogenesis and organogenesis phenomena.