Developmental Cell
Volume 44, Issue 2, 22 January 2018, Pages 165-178.e6
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Article
Engineered Tissue Folding by Mechanical Compaction of the Mesenchyme

https://doi.org/10.1016/j.devcel.2017.12.004Get rights and content
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Highlights

  • Mesenchymal condensation involves myosin II-dependent compaction of ECM

  • Reconstituted condensates compact ECM and drive curvature at tissue interfaces

  • Finite element modeling of condensation mechanics predicts tissue folding patterns

  • Arrays of condensates encode complex curvature profiles of reconstituted tissues

Summary

Many tissues fold into complex shapes during development. Controlling this process in vitro would represent an important advance for tissue engineering. We use embryonic tissue explants, finite element modeling, and 3D cell-patterning techniques to show that mechanical compaction of the extracellular matrix during mesenchymal condensation is sufficient to drive tissue folding along programmed trajectories. The process requires cell contractility, generates strains at tissue interfaces, and causes patterns of collagen alignment around and between condensates. Aligned collagen fibers support elevated tensions that promote the folding of interfaces along paths that can be predicted by modeling. We demonstrate the robustness and versatility of this strategy for sculpting tissue interfaces by directing the morphogenesis of a variety of folded tissue forms from patterns of mesenchymal condensates. These studies provide insight into the active mechanical properties of the embryonic mesenchyme and establish engineering strategies for more robustly directing tissue morphogenesis ex vivo.

Keywords

tissue engineering
mesenchymal condensation
tissue folding
mechanobiology
synthetic biology
soft matter
smart materials
soft robotics
intestinal villi

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Present address: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA

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