Table 4 Open Questions

Are there general principles that govern pattern formation?

We know of many factors that affect pattern formation (Table 2), but do these affect all communities in the same way, or is the effect specific to a particular system or environment? And, can we derive general statements regarding which factors are most important under which conditions, or do we need to re-evaluate this for each system of interest?

How do different factors affect one another?

The factors that control spatial pattern formation are connected through many interdependencies and feedback loops (Table 2, Fig. 3). Changing one factor often changes others as well, but we lack a quantitative understanding of how different factors are related.

Can we use spatial patterns to infer cell-cell interactions?

Spatial patterns are shaped by cell growth and metabolic interactions but also depend on physical properties of cells and the environment as these control how cells move. What is the relative importance of these factors? If cell-cell interactions dominate, observed patterns could be used to infer the type of metabolic interactions, but if physical effects dominate spatial patterns, such inference approaches can be misleading.

Can cells arrange themselves in a way that increases their growth rate?

A cell’s location strongly affects how well it grows. But to what extent do cells control their location? Could active motility allow cells to achieve a better arrangement? Moreover, could cells evolve towards more optimal patterns if they are co-evolved over longer periods of time, or does competition between species prevent communities from reaching such optimal arrangements?

What are the relevant spatial scales in complex communities?

Two important length scales are the interaction range and the patch size, but how are these determined? For simple systems, these length scales can be calculated from biophysical models, but are these models still valid in more complex systems?

What is the role of temporal dynamics?

The physical and chemical environments change substantially over time as cells colonize new environments and grow into dense communities. Are there general principles governing the role of temporal dynamics in pattern formation?

What is the role of cell death in shaping patterns?

Cell death due to antagonistic interactions, phages, or predation, changes the physical and chemical environment by removing cells and releasing their chemical content. Death could thus affect pattern formation by determining how and where cells can grow (see recent review by ref. ¹⁸). Can we deepen our understanding of the role of cell death in pattern formation, and understand its interdependence with the other factors?