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Proc Natl Acad Sci U S A. 2019 Mar 19;116(12):5344-5349. doi: 10.1073/pnas.1813255116. Epub 2019 Feb 28.

Theory of mechanochemical patterning in biphasic biological tissues.

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University Grenoble Alpes, CNRS, Laboratoire Interdisciplinaire de Physique, F-38000 Grenoble, France;
Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, CB3 0HE, United Kingdom;
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, United Kingdom.
Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, CB2 1QR, United Kingdom.
Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria


The formation of self-organized patterns is key to the morphogenesis of multicellular organisms, although a comprehensive theory of biological pattern formation is still lacking. Here, we propose a minimal model combining tissue mechanics with morphogen turnover and transport to explore routes to patterning. Our active description couples morphogen reaction and diffusion, which impact cell differentiation and tissue mechanics, to a two-phase poroelastic rheology, where one tissue phase consists of a poroelastic cell network and the other one of a permeating extracellular fluid, which provides a feedback by actively transporting morphogens. While this model encompasses previous theories approximating tissues to inert monophasic media, such as Turing's reaction-diffusion model, it overcomes some of their key limitations permitting pattern formation via any two-species biochemical kinetics due to mechanically induced cross-diffusion flows. Moreover, we describe a qualitatively different advection-driven Keller-Segel instability which allows for the formation of patterns with a single morphogen and whose fundamental mode pattern robustly scales with tissue size. We discuss the potential relevance of these findings for tissue morphogenesis.


morphogen transport; morphogenesis; pattern formation; poroelasticity; scaling

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