arXiv subjects

Alpha S. Yap

Publications and source records attributed to Alpha S. Yap.

4 recordsLinked to original sources

arXiv2024

Advecting Scaffolds: Controlling The Remodelling Of Actomyosin With Anillin

We propose and analyse an active hydrodynamic theory that characterises the effects of the scaffold protein anillin. Anillin is found at major sites of cortical activity, such as adherens junctions and the cytokinetic furrow, where the canonical regulator of actomyosin remodelling is the small GTPase, RhoA. RhoA acts via intermediary 'effectors' to increase both the rates of activation of myosin motors and the polymerisation of actin filaments. Anillin has been shown to scaffold this action of RhoA - improving critical rates in the signalling pathway without altering the essential biochemistry - but its contribution to the wider spatio-temporal organisation of the cortical cytoskeleton remains poorly understood. Here, we combine analytics and numerics to show how anillin can non-trivially regulate the cytoskeleton at hydrodynamic scales. At short times, anillin can amplify or dampen existing contractile instabilities, as well as alter the parameter ranges over which they occur. At long times, it can change both the size and speed of steady-state travelling pulses. The primary mechanism that underpins these behaviours is established to be the advection of anillin by myosin II motors, with the specifics relying on the values of two coupling parameters. These codify anillin's effect on local signalling kinetics and can be traced back to its interaction with the acidic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), thereby establishing a putative connection between actomyosin remodelling and membrane composition.

q-bio.SC↗

arXiv2017

Contact inhibition of locomotion and junctional mechanics guide collective cell behavior in epithelial wound repair

Epithelial tissues form physically integrated barriers against the external environment protecting organs from infection and invasion. Within each tissue, epithelial cells respond to different challenges that can potentially compromise tissue integrity. In particular, cells collectively respond by reorganizing their cell-cell junctions and migrating directionally towards the sites of injury. Notwithstanding, the mechanisms that define the spatiotemporal scales and driving forces of these collective responses remain poorly understood. To address this we first analyzed the collective response of epithelial monolayers to injury and compare the results with different computational models of epithelial cells. We found that a model that integrates the mechanics of cells at the cell-cell and cell-substrate interface as well as contact inhibition of locomotion predicts two key properties of epithelial response to injury as: 1) local relaxation of the tissue and 2) collective responses involving the elongation of cells (basal and apical regions) and extension of cryptic lamellipodia that extend up to < 3 cell diameters from the site of injury. Our results therefore highlight the integration between junctional biomechanics, cell substrate adhesion and contact inhibition of locomotion to guide the rapid collective rearrangements that are required to preserve the epithelial barrier in response to injury.

physics.bio-ph↗

arXiv2016

Contact inhibition of locomotion and mechanical cross-talk between cell-cell and cell-substrate adhesion determines the pattern of junctional tension in epithelial cell aggregates

We generated a computational approach to analyze the biomechanics of epithelial cell aggregates, either island or stripes or entire monolayers, that combines both vertex and contact-inhibition-of-locomotion models to include both cell-cell and cell-substrate adhesion. Examination of the distribution of cell protrusions (adhesion to the substrate) in the model predicted high order profiles of cell organization that agree with those previously seen experimentally. Cells acquired an asymmetric distribution of basal protrusions, traction forces and apical aspect ratios that decreased when moving from the edge to the island center. Our in silico analysis also showed that tension on cell-cell junctions and apical stress is not homogeneous across the island. Instead, these parameters are higher at the island center and scales up with island size, which we confirmed experimentally using laser ablation assays and immunofluorescence. Without formally being a 3-dimensional model, our approach has the minimal elements necessary to reproduce the distribution of cellular forces and mechanical crosstalk as well as distribution of principal stress in cells within epithelial cell aggregates. By making experimental testable predictions, our approach would benefit the mechanical analysis of epithelial tissues, especially when local changes in cell-cell and/or cell-substrate adhesion drive collective cell behavior.

physics.bio-ph↗

arXiv2013

Patterns in Space: Coordinating Adhesion and Actomyosin Contractility at E-cadherin Junctions

Cadherin adhesion receptors are fundamental determinants of tissue organization in health and disease. Increasingly, we have come to appreciate that classical cadherins exert their biological actions through active cooperation with the contractile actin cytoskeleton. Rather than being passive resistors of detachment forces, cadherins can regulate the assembly and mechanics of the contractile apparatus itself. Moreover, coordinate spatial patterning of adhesion and contractility is emerging as a determinant of morphogenesis. Here we review recent developments in cadherins and actin cytoskeleton cooperativity, by focusing on E-cadherin adhesive patterning in the epithelia. Next, we discuss the underlying principles of cellular rearrangement during Drosophila germband extension and epithelial cell extrusion, as models of how planar and apical-lateral patterns of contractility organizes tissue architecture.

q-bio.SC↗