RT Journal Article
SR Electronic
T1 Amyloid fibril-based hydrogels for high-throughput tumor spheroid modeling
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.28.424634
DO 10.1101/2020.12.28.424634
A1 Namrata Singh
A1 Komal Patel
A1 Ambuja Navalkar
A1 Pradeep Kadu
A1 Debalina Datta
A1 Debdeep Chatterjee
A1 Abhishek Shaw
A1 Sachin Jadhav
A1 Samir K. Maji
YR 2020
UL http://biorxiv.org/content/early/2020/12/29/2020.12.28.424634.abstract
AB Biomaterials mimicking extracellular matrices (ECM) for three-dimensional (3D) cultures have gained immense interest in tumor modeling and in vitro organ development. Here, we introduce versatile, thixotropic amyloid hydrogels as a bio-mimetic ECM scaffold for 3D cell culture as well as high-throughput tumor spheroid formation using a drop cast method. The unique cross-β-sheet structure, sticky surface, and thixotropicity of amyloid hydrogels allow robust cell adhesion, survival, proliferation, and migration, which are essential for 3D tumor modeling with various cancer cell types. The spheroids formed show overexpression of the signature cancer biomarkers and confer higher drug resistance compared to two-dimensional (2D) monolayer cultures. Using breast tumor tissue from mouse xenograft, we showed that these hydrogels support the formation of tumor spheroids with a well-defined necrotic core, cancer-associated gene expression, higher drug resistance, and tumor heterogeneity reminiscent of the original tumor. Altogether, we have developed a rapid and cost-effective platform for generating in vitro cancer models for the screening of anti-cancer therapeutics and developing personalized medicines.Competing Interest StatementThe authors have declared no competing interest.