Forces driving cell sorting in Hydra

Cell sorting, whereby a heterogeneous cell mixture organizes into distinct tissues, is a fundamental patterning process in development. So far, most studies of cell sorting have relied either on 2-dimensional cellular aggregates, in vitro situations that do not have a direct counterpart in vivo, or were focused on the properties of single cells. Here, we report the first multiscale experimental study on 3-dimensional regenerating Hydra aggregates, capable of reforming a full animal. By quantifying the kinematics of single cell and whole aggregate behaviors, we show that no differences in cell motility exist among cell types and that sorting dynamics follow a power law. Moreover, we measure the physical properties of separated tissues and determine their viscosities and surface tensions. Based on our experimental results and numerical simulations, we conclude that tissue interfacial tensions are sufficient to explain Hydra cell sorting. Doing so, we illustrate D’Arcy Thompson’s central idea that biological organization can be understood through physical principles, an idea which is currently re-shaping the field of developmental biology. Introduction How a pattern emerges from an initially near-uniform cell population is a question that has long fascinated biologists and physicists alike, in particular d’Arcy Thompson. In his influential 1917 book On Growth and Form (Thompson, 1992), Thompson emphasized the fact that, when one is faced with such a complex phenomenon as the form of a living organism, there can be more than one explanation, depending on the level of understanding one aims to achieve (molecular, cellular, organismal). Although evolutionary and molecular processes play key roles in morphogenesis, Thompson insisted on the importance of studying this question from a purely physical perspective: “My sole purpose here is to correlate with mathematical statement and physical law certain of the simpler outward phenomena of organic growth and structure or form [...]. But I would not for the world be thought to believe that this is the only story which Life and her Children have to tell” (Thompson, 1992). not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/142976 doi: bioRxiv preprint first posted online May. 27, 2017;