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Biomaterials. 2015 Jul;58:1-9. doi: 10.1016/j.biomaterials.2015.04.021. Epub 2015 Apr 29.

Controlled surface topography regulates collective 3D migration by epithelial-mesenchymal composite embryonic tissues.

Author information

1
Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260, USA.
2
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260, USA.
3
Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
4
Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA. Electronic address: prleduc@cmu.edu.
5
Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Department of Physical Intelligence, Max Planck Institute for Intelligent Systems, Stuttgart, Germany. Electronic address: msitti@cmu.edu.
6
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260, USA; Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA; Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: lad43@pitt.edu.

Abstract

Cells in tissues encounter a range of physical cues as they migrate. Probing single cell and collective migratory responses to physically defined three-dimensional (3D) microenvironments and the factors that modulate those responses are critical to understanding how tissue migration is regulated during development, regeneration, and cancer. One key physical factor that regulates cell migration is topography. Most studies on surface topography and cell mechanics have been carried out with single migratory cells, yet little is known about the spreading and motility response of 3D complex multi-cellular tissues to topographical cues. Here, we examine the response to complex topographical cues of microsurgically isolated tissue explants composed of epithelial and mesenchymal cell layers from naturally 3D organized embryos of the aquatic frog Xenopus laevis. We control topography using fabricated micropost arrays (MPAs) and investigate the collective 3D migration of these multi-cellular systems in these MPAs. We find that the topography regulates both collective and individual cell migration and that dense MPAs reduce but do not eliminate tissue spreading. By modulating cell size through the cell cycle inhibitor Mitomycin C or the spacing of the MPAs we uncover how 3D topographical cues disrupt collective cell migration. We find surface topography can direct both single cell motility and tissue spreading, altering tissue-scale processes that enable efficient conversion of single cell motility into collective movement.

KEYWORDS:

Cell mechanics; Microstructure; Morphogenesis; Soft tissue biomechanics; Topology

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