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Nat Commun. 2019 Jan 11;10(1):144. doi: 10.1038/s41467-018-07967-4.

Dispersible hydrogel force sensors reveal patterns of solid mechanical stress in multicellular spheroid cultures.

Author information

1
Department of Chemical Engineering, McGill University, Montréal, H3A 0C5, QC, Canada.
2
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montréal, H3A 1A3, QC, Canada.
3
Department of Oncology, McGill University, Montréal, H4A 3T2, QC, Canada.
4
Department of Biochemistry, McGill University, Montréal, H3G 1Y6, QC, Canada.
5
Department of Biomedical Engineering, University of Michigan, Ann Arbor, 48109, MI, USA.
6
Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, 30332, GA, USA.
7
Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, 14260, NY, USA.
8
Montreal Heart Institute, Montréal, H1T 1C8, QC, Canada.
9
Department of Biological and Biomedical Engineering, McGill University, Montréal, H3A 2B4, QC, Canada.
10
Department of Chemical Engineering, McGill University, Montréal, H3A 0C5, QC, Canada. chris.moraes@mcgill.ca.
11
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montréal, H3A 1A3, QC, Canada. chris.moraes@mcgill.ca.
12
Department of Biological and Biomedical Engineering, McGill University, Montréal, H3A 2B4, QC, Canada. chris.moraes@mcgill.ca.

Abstract

Understanding how forces orchestrate tissue formation requires technologies to map internal tissue stress at cellular length scales. Here, we develop ultrasoft mechanosensors that visibly deform under less than 10 Pascals of cell-generated stress. By incorporating these mechanosensors into multicellular spheroids, we capture the patterns of internal stress that arise during spheroid formation. We experimentally demonstrate the spontaneous generation of a tensional 'skin', only a few cell layers thick, at the spheroid surface, which correlates with activation of mechanobiological signalling pathways, and balances a compressive stress profile within the tissue. These stresses develop through cell-driven mechanical compaction at the tissue periphery, and suggest that the tissue formation process plays a critically important role in specifying mechanobiological function. The broad applicability of this technique should ultimately provide a quantitative basis to design tissues that leverage the mechanical activity of constituent cells to evolve towards a desired form and function.

PMID:
30635553
PMCID:
PMC6329783
DOI:
10.1038/s41467-018-07967-4
[Indexed for MEDLINE]
Free PMC Article

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