Theory of mechanochemical patterning in biphasic biological tissues

P. Recho,Adrien Hallou,É. Hannezo

Published 2018 in Proceedings of the National Academy of Sciences of the United States of America

ABSTRACT

Significance Pattern formation is a central question in developmental biology. Alan Turing proposed that this could be achieved by a diffusion-driven instability in a monophasic system consisting of two reacting chemicals. In this paper, we extend Turing’s work to a more realistic mechanochemical model of multicellular tissue, modeling also its biphasic and mechanical properties. Overcoming limitations of conventional reaction–diffusion models, we show that mechanochemical couplings between morphogen concentrations and extracellular fluid flows provide alternative, non-Turing, mechanisms by which tissues can form robust spatial patterns. 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.

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