Engineered Tissue Folding by Mechanical Compaction of the Mesenchyme

Alex J Hughes; Hikaru Miyazaki; Maxwell C Coyle; Jesse Zhang; Matthew T Laurie; Daniel Chu; Zuzana Vavrušová; Richard A Schneider; Ophir D Klein; Zev J Gartner

doi:10.1016/j.devcel.2017.12.004

Engineered Tissue Folding by Mechanical Compaction of the Mesenchyme

Dev Cell. 2018 Jan 22;44(2):165-178.e6. doi: 10.1016/j.devcel.2017.12.004. Epub 2017 Dec 28.

Authors

Affiliations

¹ Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA; Center for Cellular Construction, University of California, San Francisco, CA 94143, USA.
² 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.
³ Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
⁴ Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA; Graduate Program in Bioengineering, University of California, Berkeley, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, USA.
⁵ Department of Biochemistry and Molecular Biology, University of California, San Francisco, CA 94143, USA.
⁶ Department of Orthopaedic Surgery, University of California, San Francisco, CA 94143, USA.
⁷ Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA 94143, USA; Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco, CA 94143, USA.
⁸ Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA; Center for Cellular Construction, University of California, San Francisco, CA 94143, USA; Graduate Program in Bioengineering, University of California, Berkeley, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: zev.gartner@ucsf.edu.

Abstract

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

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Chick Embryo
Extracellular Matrix / physiology
Finite Element Analysis
Intestines / embryology
Mesoderm / anatomy & histology*
Mesoderm / cytology
Mice
Skin / embryology
Tissue Engineering*

Abstract

Publication types

MeSH terms

Grants and funding