Self-organization principles of intracellular pattern formation

Abstract

Dynamic patterning of specific proteins is essential for the spatio-temporal regulation of many important intracellular processes in prokaryotes, eukaryotes 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 Escherichia coli, Cdc42 polarization in Saccharomyces cerevisiae and the bipolar PAR protein patterns found in Caenorhabditis elegans. By analysing 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.This article is part of the theme issue ‘Self-organization in cell biology’.

A non-linear system patterns Rab5 GTPase on the membrane

“…Self-organizing systems that form spatial patterns on membranes often depend on non-linear 246 dynamics (Halatek et al, 2018). In our system, a key feature is the membrane recruitment and 247 activation of Rab5, regulated by the Rabex5/Rabaptin5 complex.…”

“…Membrane compartmentalization is of central importance for a variety of biological 31 functions at multiple scales, from sub-cellular structures to multi-cellular organisms. Processes 32 such as cell polarization, protein and lipid sorting within sub-cellular organelles or cell and 33 tissue morphogenesis depend on the emergence of patterns (Turing, 1952;Halatek et al, 2018). 34…”

Quasi-periodic migration of single cells on short microlanes

“…The cell cytoskeleton that is responsible for cell locomotion is in 51 turn regulated by intracellular signaling proteins like the Rho family of GTPases [11], 52 whose biochemical interactions have been studied both in conceptual and in detailed 53 models [12][13][14][15][16][17][18]. In general, the mass-conserving reaction-diffusion systems formed by 54 intracellular proteins can exhibit a wide variety of spatiotemporal patterns [19]. From 55 a theoretical perspective, the formation of such patterns can be understood in terms of 56 shifting local equilibria due to lateral mass redistribution between diffusively coupled 57 reactive compartments [20,21].…”

Self-organization: the fundament of cell biology

“…Currently, further advances in our understanding of the Min system would require more experimental details, such as precise rate constants, better knowledge of the molecular details underlying the cooperativity required for the theoretical approaches and further advances in the reconstituted systems to even better reflect the in vivo situation. A different approach on the theoretical description of the Min system is put forward by Frey and co-workers [9], who explain that the often-used activator -inhibitor approach, which leads to substrate depletion, is not the only way to describe reaction -diffusion systems. Instead, combining diffusion processes with general reactions that only reflect a change in conformational state of the proteins might be more appropriate for the Min system.…”

“…While Frey and co-workers [9] discuss a general approach to understanding reaction -diffusion systems, Yang & Wu [10] focus on oscillatory waves observed at the cell cortex. Their review provides a thorough discussion of the different protein networks that are known to result in cortex waves such as positive and negative feedbacks between GTPases and the emerging awareness of possible interaction between membrane curvature and actin polymerization.…”