期刊
ADVANCED MATERIALS
卷 31, 期 46, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201904580
关键词
3D cell culture; extracellular matrix; fibrillar fibronectin; protein-polymer composites; tumor microenvironment
类别
资金
- National Cancer Institute [U01CA210152]
- FFANY Shoes on Sale
- National Science Foundation [DGE 1256260]
- Department of Defense Breast Cancer Research Post-Doctoral Fellowship [W81XWH-10-1-0582]
- Biotechnology Predoctoral Research Training Program [T32 GM008353]
- NIH's Microfluidics in Biomedical Sciences Training Program [NIH NIBIB T32 EB005582]
- NIH [R01CA196018]
- lab of Diane M. Simeone
Extracellular matrix (ECM) proteins, and most prominently, fibronectin (Fn), are routinely used in the form of adsorbed pre-coatings in an attempt to create a cell-supporting environment in both two- and three-dimensional cell culture systems. However, these protein coatings are typically deposited in a form which is structurally and functionally distinct from the ECM-constituting fibrillar protein networks naturally deposited by cells. Here, the cell-free and scalable synthesis of freely suspended and mechanically robust three-dimensional (3D) networks of fibrillar fibronectin (fFn) supported by tessellated polymer scaffolds is reported. Hydrodynamically induced Fn fibrillogenesis at the three-phase contact line between air, an Fn solution, and a tessellated scaffold microstructure yields extended protein networks. Importantly, engineered fFn networks promote cell invasion and proliferation, enable in vitro expansion of primary cancer cells, and induce an epithelial-to-mesenchymal transition in cancer cells. Engineered fFn networks support the formation of multicellular cancer structures cells from plural effusions of cancer patients. With further work, engineered fFn networks can have a transformative impact on fundamental cell studies, precision medicine, pharmaceutical testing, and pre-clinical diagnostics.
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