Peptide-protein coassembling matrices as a biomimetic 3D model of ovarian cancer

Hedegaard, Clara Louise; Redondo-G�mez, Carlos; Tan, Bee Yi; Ng, Kee Woei; Loessner, Daniela; Mata, Alvaro

Abstract

Bioengineered three-dimensional (3D) matrices expand our experimental repertoire to study tumor growth and progression in a biologically relevant, yet controlled, manner. Here, we used peptide amphiphiles (PAs) to coassemble with and organize extracellular matrix (ECM) proteins producing tunable 3D models of the tumor microenvironment. The matrix was designed to mimic physical and biomolecular features of tumors present in patients. We included specific epitopes, PA nanofibers, and ECM macromolecules for the 3D culture of human ovarian cancer, endothelial, and mesenchymal stem cells. The multicellular constructs supported the formation of tumor spheroids with extensive F-actin networks surrounding the spheroids, enabling cell-cell communication, and comparative cell-matrix interactions and encapsulation response to those observed in Matrigel. We conducted a proof-of-concept study with clinically used chemotherapeutics to validate the functionality of the multicellular constructs. Our study demonstrates that peptide-protein coassembling matrices serve as a defined model of the multicellular tumor microenvironment of primary ovarian tumors.

Citation

Hedegaard, C. L., Redondo-Gómez, C., Tan, B. Y., Ng, K. W., Loessner, D., & Mata, A. (2020). Peptide-protein coassembling matrices as a biomimetic 3D model of ovarian cancer. Science Advances, 6(40), Article eabb3298. https://doi.org/10.1126/sciadv.abb3298

• Journal Article Type: Article
• Acceptance Date: Aug 20, 2020
• Online Publication Date: Oct 2, 2020
• Publication Date: Oct 1, 2020
• Deposit Date: Aug 28, 2020
• Publicly Available Date: Oct 5, 2020
• Journal: Science Advances
• Publisher: American Association for the Advancement of Science
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 40
• Article Number: eabb3298
• DOI: https://doi.org/10.1126/sciadv.abb3298
• Public URL: https://nottingham-repository.worktribe.com/output/4856130
• Publisher URL: https://advances.sciencemag.org/content/6/40/eabb3298