Regulation of Spatiotemporal Patterns by Biological Variability: General Principles and Applications to Dictyostelium discoideum

Abstract

Spatiotemporal patterns often emerge from local interactions in a self-organizing fashion. In biology, the resulting patterns are also subject to the influence of the systematic differences between the system’s constituents (biological variability). This regulation of spatiotemporal patterns by biological variability is the topic of our review. We discuss several examples of correlations between cell properties and the self-organized spatiotemporal patterns, together with their relevance for biology. Our guiding, illustrative example will be spiral waves of cAMP in a colony of Dictyostelium discoideum cells. Analogous processes take place in diverse situations (such as cardiac tissue, where spiral waves occur in potentially fatal ventricular fibrillation) so a deeper understanding of this additional layer of self-organized pattern formation would be beneficial to a wide range of applications. One of the most striking differences between pattern-forming systems in physics or chemistry and those in biology is the potential importance of variability. In the former, system components are essentially identical with random fluctuations determining the details of the self-organization process and the resulting patterns. In biology, due to variability, the properties of potentially very few cells can have a driving influence on the resulting asymptotic collective state of the colony. Variability is one means of implementing a few-element control on the collective mode. Regulatory architectures, parameters of signaling cascades, and properties of structure formation processes can be "reverse-engineered" from observed spatiotemporal patterns, as different types of regulation and forms of interactions between the constituents can lead to markedly different correlations. The power of this biology-inspired view of pattern formation lies in building a bridge between two scales: the patterns as a collective state of a very large number of cells on the one hand, and the internal parameters of the single cells on the other.

Self-organization of chemoattractant waves inDictyosteliumdepends on F-actin and cell–substrate adhesion

“…By employing perfusion and live cell imaging of cytosolic cAMP, it has been demonstrated that the onset of collective pulses of cAMP is dictated by the stochastic cAMP pulses that are self-enhanced in the population [ 18 – 20 ] and that the oscillations require removal of extracellular cAMP by secreted phosphodiesterase [ 21 ]. These studies are largely compatible with a view that oscillations and waves of cAMP can be understood in the framework of reaction–diffusion systems [ 22 ] akin to the well-studied Belousov–Zhabotinsky reaction [ 23 ].…”

Connectivity and complex systems: learning from a multi-disciplinary perspective

“…An example is strong and non-monotonous dependence of the density of spiral waves (which regulates the size of the later-stage multicellular aggregates) on the intracellular feedback loop regulating the production of the main signalling substance, cAMP (Sawai et al, 2005 ). Understanding the relationship of regulatory mechanisms and emergent, collective behaviours is an important future challenge in Systems Biology (Grace and Hütt, 2015 ).…”

Spontaneous center formation in Dictyostelium discoideum

“…On the other hand, oscillatory models require some sort of inhomogeneity to be added to the system to produce stable centers and avoid bulk oscillations. It has been shown that increasing the cell parameters along a developmental path or adding random firing decides the location of the observed patterns in an artificial way 25–28 which contrast with experimental observations showing that oscillation is a collective effect instead of the work of some specialized cells, where even the cells composing the oscillating center move continuously in and out of the signaling center 29,30 . We suggest that a more simple mechanism is also in play to produce centers for densities less than a mono-layer: the inhomogeneous cell distribution in the system is enough to create stable emitting centers.…”