Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA; Center for Cellular Construction, University of California, San Francisco, CA 94143, USA.
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA; Graduate Program in Bioengineering, University of California, Berkeley, CA, USA; Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA 94143, USA.
Dev Cell. 2018 Jan 22;44(2):165-178.e6. doi: 10.1016/j.devcel.2017.12.004. Epub 2017 Dec 28.
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.
许多组织在发育过程中会折叠成复杂的形状。在体外控制这个过程将是组织工程学的一个重要进展。我们使用胚胎组织外植体、有限元建模和 3D 细胞图案化技术，表明细胞外基质在间充质凝聚过程中的机械压实足以沿着预定轨迹驱动组织折叠。这个过程需要细胞收缩性，在组织界面产生应变，并导致围绕和在凝聚物之间的胶原排列模式。排列的胶原纤维支撑升高的张力，促进沿着可以通过建模预测的路径折叠界面。我们通过从间充质凝聚物的图案引导各种折叠组织形式的形态发生，证明了这种塑造组织界面的策略的稳健性和多功能性。这些研究为胚胎间充质的主动机械特性提供了深入的了解，并为更稳健地指导体外组织形态发生建立了工程策略。
