Approaching the Molecular Origins of Collective Dynamics in Oscillating Cell Populations This Review Comes from a Themed Issue on Genetics of System Biology Edited Oscillations in Communicating Cell Populations Molecular Interactions Cellular Interactions

From flocking birds, to organ generation, to swarming bacterial colonies, biological systems often exhibit collective behaviors. Here, we review recent advances in our understanding of collective dynamics in cell populations. We argue that understanding population-level oscillations requires examining the system under consideration at three different levels of complexity: at the level of isolated cells, homogenous populations, and spatially structured populations. We discuss the experimental and theoretical challenges this poses and highlight how new experimental techniques, when combined with conceptual tools adapted from physics, may help us overcome these challenges. Introduction Collective behaviors are ubiquitous in biological systems. At the molecular level, proteins often aggregate into self-organized structures such as spindles [1]. At the cellular level, unicellular organisms often form structured communities composed of many individuals [2–4]. At the level of organisms, birds and fish colonies exhibit dramatic emergent behaviors such as flocking [5–7] and schooling [8–10] (see Figure). Our understanding of collective behaviors in biological systems, however, is still in its infancy, highlighting the crucial need to study systems where the link between macroscopic behavior and the microscopic components that make up the system can be probed directly through experiments. This review focuses on one class of systems where such an approach is possible: the collective dynamics in cellular populations. In their natural environments, cells often undertake complex collective behaviors in response to environmental and population cues [11,12]. Thus, understanding how cells behave in the wild requires characterizing not only the behavior of isolated cells but also how environmental signals combine with cell-to-cell communication (such as quorum sensing [13] and autocrine signaling [14]) to give rise to observed behaviors at the population level. Doing so requires us to examine how the cooperative behaviors of cell colonies differ from those of isolated cells and conversely, how the properties of single cells generate and explain the observed communal behavior. The challenges inherent in this research program are summarized by Phil Anderson's famous declaration ''More is Different'' [15]—namely, systems composed of many interacting components will exhibit new emergent behaviors that cannot be understood simply by looking at the behavior of the individual components that make up the system. Whereas Anderson largely had in mind physical systems, biological systems pose additional challenges not encountered in physics. The collective behavior of cellular populations often require cells to integrate information from a wide variety of sources in order to perform a desired task such as cellular …