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

• Authors: Siarheia Hladyshau, Georgia Institute of Technology; Mary Kho, Georgia Institute of Technology; Shuyi Nie, Georgia Institute of Technology; Denis Tsygankov, Emory University
• Journal Title: SCIENTIFIC REPORTS
• Volume: Volume 11, Number 1
• Publisher: NATURE PORTFOLIO | 2021-09-30, Pages 19512-19512
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1038/s41598-021-99029-x
• Subjects: Engineering, Biomedical; Biology, General
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; PATTERN-FORMATION; GTPASES; DYNAMICS; POLARITY; SYSTEMS; MASS

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.