Biology subjects

Staddon, M.

Publications and source records attributed to Staddon, M..

3 recordsLinked to original sources

bioRxiv2021

Asymmetric Contraction of Adherens Junctions arises through RhoA and E-cadherin feedback

Tissue morphogenesis often arises from the culmination of discrete changes in cell-cell junction behaviors, namely ratcheted junction contractions that lead to collective cellular rearrangements. Mechanochemical signaling in the form of RhoA underlies these ratcheted contractions, which occur asymmetrically as one highly motile vertex contracts toward a relatively less motile tricellular vertex. The underlying mechanisms driving asymmetric vertex movement remains unknown. Here, we use optogenetically controlled RhoA in model epithelia together with biophysical modeling to uncover the mechanism lending to asymmetric vertex motion. We find that both local and global RhoA activation leads to increases in junctional tension, thereby facilitating vertex motion. RhoA activation occurs in discrete regions along the junction and is skewed towards the less-motile vertex. At these less-motile vertices, E-cadherin acts as an opposing factor to limit vertex motion through increased frictional drag. Surprisingly, we uncover a feedback loop between RhoA and E-cadherin, as regional optogenetic activation of specified junctional zones pools E-cadherin to the location of RhoA activation. Incorporating this circuit into a mathematical model, we find that a positive feedback between RhoA-mediated tension and E-cadherin-induced frictional drag on tricellular vertices recapitulates experimental data. As such, the location of RhoA determines which vertex is under high tension, pooling E-cadherin and increasing the frictional load at the tricellular vertex to limit its motion. This feedback drives a tension-dependent intercellular "clutch" at tricellular vertices which stabilizes vertex motion upon tensional load.

cell biology↗

bioRxiv2020

Hindbrain neuropore tissue geometry determines asymmetric cell-mediated closure dynamics

Gap closure is a common morphogenetic process. In mammals, failure to close the embryonic hindbrain neuropore (HNP) gap causes fatal anencephaly. We observed that surface ectoderm cells surrounding the mouse HNP assemble high-tension actomyosin purse-strings at their leading edge and establish the initial contacts across the embryonic midline. The HNP gap closes asymmetrically, faster from its rostral than caudal extreme, while maintaining an elongated aspect ratio. Cell-based physical modelling identifies two closure mechanisms sufficient to describe tissue-level HNP closure dynamics; purse-string contraction and directional cell crawling. Combining both closure mechanisms hastens gap closure and produces a constant rate of gap shortening. Purse-string contraction reduces, whereas crawling increases gap aspect ratio, and their combination maintains it. Closure rate asymmetry can be explained by embryo tissue geometry, namely a narrower rostral gap apex. At the cellular level, our model predicts highly directional cell migration with a constant rate of cells leaving the HNP rim. These behaviours are reproducibly live-imaged in mouse embryos. Thus, mammalian embryos coordinate cellular and tissue-level mechanics to achieve this critical gap closure event.

biophysics↗

bioRxiv2020

Tissue pressure and cell traction compensate to drive robust aggregate spreading

In liquid droplets, the balance of interfacial energies and substrate elasticity determines the shape of the droplet and the dynamics of wetting. In living cells, interfacial energies are not constant, but adapt to the mechanics of their environment. As a result, the forces driving the dynamics of wetting for cells and tissues are unclear and may be context specific. In this work, using a combination of experimental measurements and modeling, we show the surface tension of cell aggregates, as models of active liquid droplets, depends upon the size of the aggregate and the magnitude of applied load, which alters the wetting dynamics. Upon wetting rigid substrates, traction stresses are elevated at the boundary, and tension drives forward motion. By contrast, upon wetting compliant substrates, traction forces are attenuated, yet wetting occurs at a comparable rate. In this case, capillary forces at the contact line are elevated and aggregate surface tension contributes to strong outward, pressure-driven cellular flows. Thus, cell aggregates adapt to the mechanics of their environments, using pressure and traction as compensatory mechanisms to drive robust wetting.

biophysics↗