Matrix degradability controls multicellularity of 3D cell migration

Britta Trappmann (), Brendon M. Baker, William J. Polacheck, Colin K. Choi, Jason A. Burdick and Christopher S. Chen ()
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Britta Trappmann: Boston University
Brendon M. Baker: Boston University
William J. Polacheck: Boston University
Colin K. Choi: Boston University
Jason A. Burdick: University of Pennsylvania
Christopher S. Chen: Boston University

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: Abstract A major challenge in tissue engineering is the development of materials that can support angiogenesis, wherein endothelial cells from existing vasculature invade the surrounding matrix to form new vascular structures. To identify material properties that impact angiogenesis, here we have developed an in vitro model whereby molded tubular channels inside a synthetic hydrogel are seeded with endothelial cells and subjected to chemokine gradients within a microfluidic device. To accomplish precision molding of hydrogels and successful integration with microfluidics, we developed a class of hydrogels that could be macromolded and micromolded with high shape and size fidelity by eliminating swelling after polymerization. Using this material, we demonstrate that matrix degradability switches three-dimensional endothelial cell invasion between two distinct modes: single-cell migration and the multicellular, strand-like invasion required for angiogenesis. The ability to incorporate these tunable hydrogels into geometrically constrained settings will enable a wide range of previously inaccessible biomedical applications.

Date: 2017
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DOI: 10.1038/s41467-017-00418-6

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