Spatiotemporal development of coexisting wave domains of Rho activity in the cell cortex

Siarhei Hladyshau,Mary Kho,Shuyi Nie,Denis Tsygankov

doi:10.1038/s41598-021-99029-x

Siarhei Hladyshau, Mary Kho + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-99029-x

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Abstract

The Rho family GTPases are molecular switches that regulate cytoskeletal dynamics and cell movement through a complex spatiotemporal organization of their activity. In Patiria miniata (starfish) oocytes under in vitro experimental conditions (with overexpressed Ect2, induced expression of Δ90 cyclin B, and roscovitine treatment), such activity generates multiple co-existing regions of coherent propagation of actin waves. Here we use computational modeling to investigate the development and properties of such wave domains. The model reveals that the formation of wave domains requires a balance between the activation and inhibition in the Rho signaling motif. Intriguingly, the development of the wave domains is preceded by a stage of low-activity quasi-static patterns, which may not be readily observed in experiments. Spatiotemporal patterns of this stage and the different paths of their destabilization define the behavior of the system in the later high-activity (observable) stage. Accounting for a strong intrinsic noise allowed us to achieve good quantitative agreement between simulated dynamics in different parameter regimes of the model and different wave dynamics in Patiria miniata and wild type Xenopus laevis (frog) data. For quantitative comparison of simulated and experimental results, we developed an automated method of wave domain detection, which revealed a sharp reversal in the process of pattern formation in starfish oocytes. Overall, our findings provide an insight into spatiotemporal regulation of complex and diverse but still computationally reproducible cell-level actin dynamics.

Highlights

The Rho family GTPases are molecular switches that regulate cytoskeletal dynamics and cell movement through a complex spatiotemporal organization of their activity
We showed that the development of wave domains has a non-trivial temporal progression
Before wave domains become clearly visible, the system goes through a period of pattern formation with activity level orders of magnitude smaller than the activity at the later stage, the stage that we can compare with the experimental observations of Bement et al.[31]

Summary

Introduction

The Rho family GTPases are molecular switches that regulate cytoskeletal dynamics and cell movement through a complex spatiotemporal organization of their activity. The arrest of Cdk[1] inactivation by ∆90 cyclin B terminates wave dynamics because Cdk[1] inactivation is needed for the excitability of the cell cortex (see Ref.[31] for details) Under these conditions, the pharmacological treatment of cells with roscovitine (that inhibits Cdk1) activates cortical waves that propagate on the whole cell scale (because of Ect[2] overexpression) and are not perturbed by the formation of cytokinetic furrow. The focus of this modeling effort was to investigate the formation of a static cytokinetic furrow in the presence of dynamics waves This model was not applied to describe wave domains and the process of their development. To study the details and the scope of possible transient behaviors (far from a steady state), we still have to rely on a systematic analysis of the parameter space using simulations

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