Mechanophenotyping of 3D multicellular clusters using displacement arrays of rendered tractions
| Autor: | Thomas M. Valentin, Mohak Patel, Ian Y. Wong, Evelyn Kendall Williams, Christian Franck, Amanda Khoo, Susan E. Leggett, Lena Gamboa |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Materials science Epithelial-Mesenchymal Transition Primary Cell Culture 02 engineering and technology Collective migration Cell Line Extracellular matrix 03 medical and health sciences Mechanobiology 0302 clinical medicine Cell Movement Spheroids Cellular Cluster (physics) Humans Epithelial–mesenchymal transition Precision Medicine 030304 developmental biology 0303 health sciences Multidisciplinary Tissue Scaffolds Chemistry Disease progression Human patient Epithelial Cells Hydrogels 021001 nanoscience & nanotechnology Biomechanical Phenomena Multicellular organism 030104 developmental biology Phenotype Preclinical testing 030220 oncology & carcinogenesis Physical Sciences Biophysics Collagen Drug Screening Assays Antitumor 0210 nano-technology Fibroins |
| Zdroj: | Proc Natl Acad Sci U S A |
| Popis: | 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 anti-migration 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 using drugs, biasing towards 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. |
| Databáze: | OpenAIRE |
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