PT  - JOURNAL ARTICLE
AU  - Giovanna De Palo
AU  - Darvin Yi
AU  - Robert G. Endres
TI  - A Critical-like Collective State Leads to Long-range Cell Communication in <em>Dictyostelium discoideum</em> Aggregation
AID  - 10.1101/086538
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 086538
4099  - http://biorxiv.org/content/early/2016/11/08/086538.short
4100  - http://biorxiv.org/content/early/2016/11/08/086538.full
AB  - The transition from single-cell to multicellular behavior is important in early development but rarely studied. The starvation-induced aggregation of the social amoeba Dictyostelium discoideum into a multicellular slug is known to result from single-cell chemotaxis towards emitted pulses of cyclic adeno-sine monophosphate (cAMP). However, how exactly do transient short-range chemical gradients lead to coherent collective movement at a macroscopic scale? Here, we use a multiscale model verified by quantitative microscopy to describe wide-ranging behaviors from chemotaxis and excitability of individual cells to aggregation of thousands of cells. To better understand the mechanism of long-range cell-cell communication and hence aggregation, we analyze cell-cell correlations, showing evidence for self-organization at the onset of aggregation (as opposed to following a leader cell). Surprisingly, cell collectives, despite their finite size, show features of criticality known from phase transitions in physical systems. Application of external cAMP perturbations in our simulations near the sensitive critical point allows steering cells into early aggregation and towards certain locations but not once an aggregation center has been chosen.Author Summary Cells are often coupled to each other in cell collectives, such as aggregates during early development, tissues in the developed organism, and tumors in disease. How do cells communicate over macroscopic distances much larger than their typical cell-cell neighboring distance to decide how they should behave? Here, we develop a multiscale model of social amoeba, spanning behavior from individuals to thousands of cells. We show that local cell-cell coupling via secreted chemicals may be tuned to a critical value, resulting in emergent long-range communication and heightened sensitivity. Hence, these aggregates are remarkably similar to bacterial biofilms and neuronal networks, all communicating in a pulse-like fashion. Similar organizing principles may also aid our understanding of the remarkable robustness in cancer development.