Actin network heterogeneity tunes activator-inhibitor dynamics at the cell cortex
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Biological systems can display diverse patterns of self-organization, even when built on conserved networks of interaction between molecular species. In these cases, reaction-diffusion equations provide a valuable tool to learn how new dynamics could emerge from quantitative tuning of parameters. Bringing these models into quantitative correspondence with biological data remains an outstanding challenge, especially when the data manifest heterogeneities that are difficult to account for mathematically. One particular example occurs in cell biology, where the membrane-bound regulatory protein RhoA interacts with the filamentous actin cortex in an activator-inhibitor loop. Though this core biochemical circuit is conserved across multiple cell types in different organisms, it produces different patterns of RhoA activity in different contexts, from traveling waves in starfish to transient pulses in C. elegans . To understand how this variation emerges, we develop an activator-inhibitor model that accounts explicitly for actin assembly and heterogeneity. By fitting the model to summary statistics of experimental data, subject to known parameter constraints, we show that F-actin assembly dynamics tune the spatiotemporal patterns of RhoA activity. A minimal representation of these dynamics reveals how directional transport (via polymerization) combines with stochasticity in F-actin number and orientation to produce the observed patterns. This work sheds light on how phenotypic diversity arises from heterogeneity and anisotropy, with important implications for the next generation of activator-inhibitor models.
Significance
To divide, move, and polarize, cells must self-organize their constituent proteins into large-scale patterns with varied spatiotemporal character. The design principles of this process remain poorly understood, primarily because quantitatively matching mathematical models to experimental data is difficult. Here we consider pattern formation from two constituents on the cell cortex: the regulatory protein RhoA and actin filaments. Using a mathematical model, constrained quantitatively by data from multiple organisms, we show how diversity in RhoA activity can arise from intra- and inter-organismal changes in actin filament architecture and assembly dynamics. Our results reveal general principles for pattern formation at the cortex, and our combination of data analysis, modeling, and parameter inference provides a broadly-applicable, interdisciplinary methodology to unravel mechanisms of self-organization.
