Tissue Folding by Mechanical Compaction of the Mesenchyme

Abstract

Many tissues fold during development into complex shapes. Engineering 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 a mechanical compaction of the ECM during mesenchymal condensation can drive tissue folding along programmed trajectories. The process requires cell contractility, generates strains at nearby tissue interfaces, and causes specific 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 finite element 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 engineered patterns of mesenchymal condensates. These studies provide insight into the active mechanical properties of the embryonic mesenchyme and establish entirely new strategies for more robustly directing tissue morphogenesis ex vivo, without genetic engineering.