Spatiotemporal variation of endogenous cell-generated stresses within 3D multicellular spheroids

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Adam A. Lucio - , University of California at Santa Barbara (Author)
  • Alessandro Mongera - , University of California at Santa Barbara (Author)
  • Elijah Shelton - , University of California at Santa Barbara (Author)
  • Renwei Chen - , University of California at Santa Barbara (Author)
  • Adele M. Doyle - , University of California at Santa Barbara (Author)
  • Otger Campàs - , University of California at Santa Barbara (Author)

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

Original languageEnglish
Article number12022
JournalScientific reports
Volume7
Issue number1
Publication statusPublished - 1 Dec 2017
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 28931891
ORCID /0000-0003-4204-3642/work/158767727

Keywords

ASJC Scopus subject areas