Many biological tissues are viscoelastic, behaving as elastic solids on short timescales and fluids on long timescales. This collective mechanical behaviour enables and helps to guide pattern formation and tissue layering. Here, we investigate the mechanical properties of three-dimensional tissue explants from zebrafish embryos by analysing individual cell tracks and macroscopic mechanical response. We find that the cell dynamics inside the tissue exhibit features of supercooled fluids, including subdiffusive trajectories and signatures of caging behaviour. We develop a minimal, three-parameter mechanical model for these dynamics, which we calibrate using only information about cell tracks. This model generates predictions about the macroscopic bulk response of the tissue (with no fit parameters) that are verified experimentally, providing a strong validation of the model. The best-fit model parameters indicate that although the tissue is fluid-like, it is close to a glass transition, suggesting that small changes to single-cell parameters could generate a significant change in the viscoelastic properties of the tissue. These results provide a robust framework for quantifying and modelling mechanically driven pattern formation in tissues.

SUMMARYChanges in animal behavior resulting from genetic or chemical intervention are frequently used for phenotype characterizations. The majority of these studies are qualitative in nature, especially in systems that go beyond the classical model organisms. Here, we introduce a quantitative method to characterize behavior in the freshwater planarian Schmidtea mediterranea. Wild-type locomotion in confinement was quantified using a wide set of parameters, and the influences of intrinsic intra-worm versus interworm variability on our measurements was studied. We also examined the effect of substrate, confinement geometry and the interactions with the boundary on planarian behavior. The method is based on a simple experimental setup, using automated center-of-mass tracking and image analysis, making it an easily implemented alternative to current methods for screening planarian locomotion phenotypes. As a proof of principle, two drug-induced behavioral phenotypes were generated to show the capacity of this method. Supplementary material available online at

Asexual reproduction in multicellular organisms is a complex biophysical process that is not yet well understood quantitatively. Here, we report a detailed population study for the asexual freshwater planarian Schmidtea mediterranea, which can reproduce via transverse fission due to a large stem cell contingent. Our long-term observations of isolated non-interacting planarian populations reveal that the characteristic fission waiting time distributions for head and tail fragments differ significantly from each other. The stochastic fission dynamics of tail fragments exhibits non-negligible memory effects, implying that an accurate mathematical description of future data should be based on non-Markovian tree models. By comparing the effective growth of non-interacting planarian populations with those of self-interacting populations, we are able to quantify the influence of interactions between flatworms and physical conditions on the population growth. A surprising result is the non-monotonic relationship between effective population growth rate and nutrient supply: planarians exhibit a tendency to become 'obese' if the feeding frequency exceeds a critical level, resulting in a decreased reproduction activity. This suggests that these flatworms, which possess many genes homologous to those of humans, could become a new model system for studying dietary effects on reproduction and regeneration in multicellular organisms.

Dynamins are GTPases that are required for separation of vesicles from the plasma membrane and thus are key regulators of endocytosis in eukaryotic cells. This role for dynamin proteins is especially crucial for the proper function of neurons, where they ensure that synaptic vesicles and their neurotransmitter cargo are recycled in the presynaptic cell. Here we have characterized the dynamin protein family in the freshwater planarian Schmidtea mediterranea and showed that it possesses six dynamins with tissue specific expression profiles. Of these six planarian homologs, two are necessary for normal tissue homeostasis, and the loss of another, Smed-dynA-1, leads to an abnormal behavioral phenotype, which we have quantified using automated center of mass tracking. Smed-dynA-1 is primarily expressed in the planarian nervous system and is a functional homolog of the mammalian Dynamin I. The distinct expression profiles of the six dynamin genes makes planarians an interesting new system to reveal novel dynamin functions, which may be determined by their differential tissue localization. The observed complexity of neurotransmitter regulation combined with the tools of quantitative behavioral assays as a functional readout for neuronal activity, renders planarians an ideal system for studying how the nervous system controls behavior.

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