Mechanophenotyping of 3D multicellular clusters using displacement arrays of rendered tractions

Susan E. Leggett, Mohak Patel, Thomas M. Valentin, Lena Gamboa, Amanda S. Khoo, Evelyn Kendall Williams, Christian Franck, Ian Y. Wong

Research output: Contribution to journalArticlepeer-review


Epithelial tissues mechanically deform the surrounding extracellular matrix during embryonic development, wound repair, and tumor invasion. Ex vivo measurements of such multicellular tractions within three-dimensional (3D) biomaterials could elucidate collective dissemination during disease progression and enable preclinical testing of targeted antimigration therapies. However, past 3D traction measurements have been low throughput due to the challenges of imaging and analyzing information-rich 3D material deformations. Here, we demonstrate a method to profile multicellular clusters in a 96-well-plate format based on spatially heterogeneous contractile, protrusive, and circumferential tractions. As a case study, we profile multicellular clusters across varying states of the epithelial-mesenchymal transition, revealing a successive loss of protrusive and circumferential tractions, as well as the formation of localized contractile tractions with elongated cluster morphologies. These cluster phenotypes were biochemically perturbed by using drugs, biasing toward traction signatures of different epithelial or mesenchymal states. This higher-throughput analysis is promising to systematically interrogate and perturb aberrant mechanobiology, which could be utilized with human-patient samples to guide personalized therapies.

Original languageEnglish (US)
Pages (from-to)5655-5663
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number11
StatePublished - Mar 17 2020
Externally publishedYes


  • 3D culture
  • Cell-matrix interactions
  • Collective migration
  • Epithelial-mesenchymal transition

ASJC Scopus subject areas

  • General


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