Chemical and mechanical pattern formation is fundamental during embryogenesis and tissue development. Yet, the underlying molecular and cellular mechanisms are still elusive in many cases. Most current theories assume that tissue development is driven by chemical processes: either as a sequence of chemical patterns each depending on the previous one, or by patterns spontaneously arising from specific chemical interactions (such as “Turing-patterns”). Within both theories, mechanical patterns are usually regarded as passive by-products of chemical pre-patters. However, several experiments question these theories, and an increasing number of studies shows that tissue mechanics can actively influence chemical patterns during development. In this study, we thus focus on the interplay between chemical and mechanical processes during tissue development. On one hand, based on recent experimental data, we develop new mechanochemical simulation models of evolving tissues, in which the full 3D representation of the tissue appears to be critical for obtaining a realistic mechanochemical behaviour. The presented modelling approach is flexible and numerically studied using state of the art finite element methods. Thus, it may serve as a basis to combine simulations with new experimental methods in tissue development. On the other hand, we apply the developed approach and demonstrate that even simple interactions between tissue mechanics and chemistry spontaneously lead to robust and complex mechanochemical patterns. Especially, we demonstrate that the main contradictions arising in the framework of purely chemical theories are naturally and automatically resolved using the mechanochemical patterning theory.

BackgroundDuring embryogenesis, chemical (morphogen) and mechanical patterns develop within tissues in a self-organized way. More than 60 years ago, Turing proposed his famous reaction-diffusion model for such processes, assuming chemical interactions as the main driving force in tissue patterning. However, experimental identification of corresponding molecular candidates is still incomplete. Recent results suggest that beside morphogens, also tissue mechanics play a significant role in these patterning processes.ResultsCombining continuous finite strain with discrete cellular tissue models, we present and numerically investigate mechanochemical processes, in which morphogen dynamics and tissue mechanics are coupled by feedback loops. We consider three different mechanical cues involved in such feedbacks: strain, stress, and compression. Based on experimental results, for each case, we present a feedback loop spontaneously creating robust mechanochemical patterns. In contrast to Turing-type models, simple mechanochemical interaction terms are sufficient to create de novo patterns.ConclusionsOur results emphasize mechanochemical processes as possible candidates controlling different steps of embryogenesis. To motivate further experimental research discovering related mechanisms in living tissues, we also present predictive in silicio experiments.ReviewersReviewer 1 - Marek Kimmel; Reviewer 2 - Konstantin Doubrovinski (nominated by Ned Wingreen); Reviewer 3 - Jun Allard (nominated by William Hlavacek).