Engineered Tissue Folding by Mechanical Compaction of the Mesenchyme

• Published in: Developmental cell Vol. 44; no. 2; pp. 165 - 178.e6
• Main Authors: Hughes, Alex J., Miyazaki, Hikaru, Coyle, Maxwell C., Zhang, Jesse, Laurie, Matthew T., Chu, Daniel, Vavrušová, Zuzana, Schneider, Richard A., Klein, Ophir D., Gartner, Zev J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.01.2018
• Subjects: Animals; Chick Embryo; Extracellular Matrix - physiology; Finite Element Analysis; intestinal villi; Intestines - embryology; mechanobiology; mesenchymal condensation; Mesoderm - anatomy & histology; Mesoderm - cytology; Mice; Skin - embryology; smart materials; soft matter; soft robotics; synthetic biology; Tissue Engineering; tissue folding; mechanobiology; synthetic biology; tissue engineering; soft matter; tissue folding; soft robotics; smart materials; mesenchymal condensation; intestinal villi
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2017.12.004

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. [Display omitted] •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 A key challenge for tissue engineering is to harness the organizational principles that generate complex tissue topography in vivo. Hughes et al. find that mesenchymal compaction processes are sufficient to generate curvature at tissue interfaces and develop a framework to engineer curvature trajectories of reconstituted tissues via patterns of mesenchymal condensates.