No abstract

SignificanceMost living systems, from individual cells to tissues and swarms, display collective self-organization on length scales that are much larger than those of the individual units that drive this organization. A fundamental challenge is to understand how properties of microscopic components determine macroscopic, multicellular biological function. Our study connects intracellular physiology to macroscale collective behaviors during multicellular development, spanning five orders of magnitude in length and six orders of magnitude in time, using bacterial swarming as a model system. This work is enabled by a high-throughput adaptive microscopy technique, which we combined with genetics, machine learning, and mathematical modeling to reveal the phase diagram of bacterial swarming and that cell–cell interactions within each swarming phase are dominated by mechanical interactions.

During development, gene expression regulates cell mechanics and shape to sculpt tissues. Epithelial folding proceeds through distinct cell shape changes that occur simultaneously in different regions of a tissue. Here, using quantitative imaging in Drosophila melanogaster, we investigate how patterned cell shape changes promote tissue bending during early embryogenesis. We find that the transcription factors Twist and Snail combinatorially regulate a multicellular pattern of lateral F-actin density that differs from the previously described myosin-2 gradient. This F-actin pattern correlates with whether cells apically constrict, stretch, or maintain their shape. We show that the myosin-2 gradient and F-actin depletion do not depend on force transmission, suggesting that transcriptional activity is required to create these patterns. The myosin-2 gradient width results from a gradient in RhoA activation that is refined through the balance between RhoGEF2 and the RhoGAP C-GAP. Our experimental results and simulations of a 3D elastic shell model show that tuning gradient width regulates tissue curvature.

In experiments with the photosensitive Belousov-Zhabotinsky reaction (PBZR) we found a stable three-dimensional organizing center that periodically emits trigger waves of chemical concentration. The experiments are performed in a parameter regime with negative line tension using an open gel reactor to maintain stationary non-equilibrium conditions. The observed periodic wave source is formed by a scroll ring stabilized due to its interaction with a no-flux boundary. Sufficiently far from the boundary, the scroll ring expands and undergoes the negative line tension instability before it finally develops into scroll wave turbulence. Our experimental results are reproduced by numerical integration of the modified Oregonator model for the PBZR. Stationary and breathing self-organized pacemakers have been found in these numerical simulations. In the latter case, both the radius of the scroll ring and the distance of its filament plane to the no-flux boundary after some transient undergo undamped stable limit cycle oscillations. So far, in contrary to their stationary counterpart, the numerically predicted breathing autonomous pacemaker has not been observed in the chemical experiment.

Chemical oscillators with a broad frequency distribution are photochemically coupled in network topologies. Experiments and simulations show that the network synchronization occurs by phase-lag synchronization of clusters of oscillators with zero- or nearly zero-lag synchronization. Symmetry also plays a role in the synchronization, the extent of which is explored as a function of coupling strength, frequency distribution, and the highest frequency oscillator location. The phase-lag synchronization occurs through connected synchronized clusters, with the highest frequency node or nodes setting the frequency of the entire network. The synchronized clusters successively "fire," with a constant phase difference between them. For low heterogeneity and high coupling strength, the synchronized clusters are made up of one or more clusters of nodes with the same permutation symmetries. As heterogeneity is increased or coupling strength decreased, the phase-lag synchronization occurs partially through clusters of nodes sharing the same permutation symmetries. As heterogeneity is further increased or coupling strength decreased, partial synchronization and, finally, independent unsynchronized oscillations are observed. The relationships between these classes of behavior are explored with numerical simulations, which agree well with the experimentally observed behavior.