Abstract

Multicellular spheroids serve as an excellent platform to study tissue behavior and tumor growth in a controlled, three-dimensional (3D) environment. While molecular and cellular studies have long used this platform to study cell behavior in 3D, only recently have studies using multicellular spheroids shown an important role for the mechanics of the microenvironment in a wide range of cellular processes, including during tumor progression. Despite the well-established relevance of mechanical cues to cell behavior and the numerous studies on mechanics using 2D cell culture systems, the spatial and temporal variations in endogenous cellular forces within growing multicellular aggregates remain unknown. Using cell-sized oil droplets with controlled physicochemical properties as force transducers in mesenchymal cell aggregates, we show that the magnitude of cell-generated stresses varies only weakly with spatial location within the spherical aggregate, but it increases considerably over time during aggregate compaction and growth. Moreover, our results indicate that the temporal increase in cellular stresses is due to increasing cell pulling forces transmitted via integrin-mediated cell adhesion, consistent with the need for larger intercellular pulling forces to compact cell aggregates.

Details

Title
Spatiotemporal variation of endogenous cell-generated stresses within 3D multicellular spheroids
Author
Lucio, Adam A 1 ; Mongera, Alessandro 1   VIAFID ORCID Logo  ; Shelton, Elijah 1 ; Chen, Renwei 2 ; Doyle, Adele M 3 ; Campàs, Otger 4   VIAFID ORCID Logo 

1  Department of Mechanical Engineering, University of California, Santa Barbara, California, USA; California NanoSystems Institute, University of California, Santa Barbara, California, USA 
2  Department of Mechanical Engineering, University of California, Santa Barbara, California, USA; California NanoSystems Institute, University of California, Santa Barbara, California, USA; Center for Bioengineering, University of California, Santa Barbara, California, USA 
3  Department of Mechanical Engineering, University of California, Santa Barbara, California, USA; California NanoSystems Institute, University of California, Santa Barbara, California, USA; Center for Bioengineering, University of California, Santa Barbara, California, USA; Neuroscience Research Institute, University of California, Santa Barbara, California, USA 
4  Department of Mechanical Engineering, University of California, Santa Barbara, California, USA; California NanoSystems Institute, University of California, Santa Barbara, California, USA; Center for Bioengineering, University of California, Santa Barbara, California, USA; Department of Molecular, Cell and Developmental Biology, University of California, Santa Barbara, California, USA 
Pages
1-11
Publication year
2017
Publication date
Sep 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-017-12363-x
ProQuest document ID
1954982157
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.