Self-organization principles of intracellular pattern formation

TL;DR

This paper reviews models of intracellular protein pattern formation, emphasizing that self-organization relies on protein redistribution and conformational cycling, with mass-conserving reaction-diffusion equations as a key framework.

Contribution

It provides a theoretical perspective on general principles of intracellular pattern formation, challenging traditional concepts like activators and inhibitors.

Findings

Mass-conserving reaction-diffusion equations are most suitable for modeling.

Directed transport via cytosolic diffusion is fundamental.

Self-organization is driven by establishing and maintaining directed transport.

Abstract

Dynamic patterning of specific proteins is essential for the spatiotemporal regulation of many important intracellular processes in procaryotes, eucaryotes, and multicellular organisms. The emergence of patterns generated by interactions of diffusing proteins is a paradigmatic example for self-organization. In this article we review quantitative models for intracellular Min protein patterns in E. coli, Cdc42 polarization in S. cerevisiae, and the bipolar PAR protein patterns found in C. elegans. By analyzing the molecular processes driving these systems we derive a theoretical perspective on general principles underlying self-organized pattern formation. We argue that intracellular pattern formation is not captured by concepts such as "activators"', "inhibitors", or "substrate-depletion". Instead, intracellular pattern formation is based on the redistribution of proteins by cytosolic diffusion, and the cycling of proteins between distinct conformational states. Therefore, mass-conserving reaction-diffusion equations provide the most appropriate framework to study intracellular pattern formation. We conclude that directed transport, e.g. cytosolic diffusion along an actively maintained cytosolic gradient, is the key process underlying pattern formation. Thus the basic principle of self-organization is the establishment and maintenance of directed transport by intracellular protein dynamics.