Diffusive coupling of two well-mixed compartments elucidates elementary principles of protein-based pattern formation

TL;DR

This paper uses a simplified two-compartment model to analyze protein pattern formation in cells, revealing fundamental principles and common features in phase space that underlie diverse biological oscillations.

Contribution

It introduces a phase-portrait analysis of coupled compartments to understand protein pattern formation, linking cell polarity oscillations to relaxation oscillations in a minimal model.

Findings

Min oscillations are relaxation oscillations of MinD polarity.

Pattern formation principles depend on parameters, not just network topology.

Phase portraits reveal universal features in protein pattern dynamics.

Abstract

Spatial organization of proteins in cells is important for many biological functions. In general, the nonlinear, spatially coupled models for protein-pattern formation are only accessible to numerical simulations, which has limited insight into the general underlying principles. To overcome this limitation, we adopt the setting of two diffusively coupled, well-mixed compartments that represents the elementary feature of any pattern -- an interface. For intracellular systems, the total numbers of proteins are conserved on the relevant timescale of pattern formation. Thus, the essential dynamics is the redistribution of the globally conserved mass densities between the two compartments. We present a phase-portrait analysis in the phase-space of the redistributed masses that provides insights on the physical mechanisms underlying pattern formation. We demonstrate this approach for several paradigmatic model systems. In particular, we show that the pole-to-pole Min oscillations in Escherichia coli are relaxation oscillations of the MinD polarity orientation. This reveals a close relation between cell polarity oscillatory patterns in cells. Critically, our findings suggest that the design principles of intracellular pattern formation are found in characteristic features in these phase portraits (nullclines and fixed points). These features are not uniquely determined by the topology of the protein-interaction network but depend on parameters (kinetic rates, diffusion constants) and distinct networks can give rise to equivalent phase portrait features.