No abstract

In this work we created electrospun fibrous scaffolds with random and aligned fiber orientations in order to mimic the 3D structure of the natural extracellular matrix (ECM). The rigidity and topography of the ECM environment have been reported to alter cancer cell behavior. But the complexity of the in vivo system makes it difficult to isolate and study such extracellular topographical cues that trigger cancer cells’ response. Breast cancer cells were cultured on these fibrous scaffolds for 3–5 days. The cells showed elongated spindle-like morphology in the aligned fibers whereas kept mostly flat stellar shape in the random fibers. Gene expression profiling of these cells post seeding, showed up-regulation of transforming growth factor β-1 (TGFβ-1) along with other mesenchymal biomarkers, suggesting that these cells are undergoing epithelial-mesenchymal transitions in response to the polymer scaffold. The results of this study indicate that the topographical cue may play a significant role in tumor progression.

Turnip yellow mosaic virus (TYMV) is an icosahedral plant virus with a diameter of 28-30 nm that can be isolated in gram quantities from turnip or Chinese cabbage inexpensively. In this study, TYMV combined with spatially addressable surface chemistries was selected as a prototype bionanoparticle for modulating patterns of cell adhesion, morphology, and proliferation. We exploited the chemical reactivity of TYMV using the mild conditions of Cu(I) catalyzed azide-alkyne cycloaddition (CuAAC) reaction, the best example of "click" chemistry. Oligo-ethylene glycol (OEG) short chain, coumarintriazole, and RGD-containing peptide were grafted on the surface of TYMV via carbodiimide activation and CuAAC reaction. The bioconjugation to intact viral particles was confirmed by MS, TEM, FPLC, and SDS-PAGE with fluorescence visualization analysis. Therefore, this method is a generally useful means of incorporating various types of functionalities onto the TYMV surface. Further studies were done to learn the behavior of NIH-3T3 fibroblast cells on the modified or unmodified TYMV surfaces. OEG-modified TYMV surfaces retarded cell attachment and growth, while cell adhesion, spreading, and proliferation were dramatically enhanced on RGD-modified TYMV surfaces. Compared with RGD immobilized 3-aminopropyltriethoxysilane-coated glass surface, the cells are more ready to spread fully and proliferate on TYMV-RGD coated surface, which thus provides a more cell-friendly environment with nanometer-scale surface features. This illustrates the potential application of plant virus based materials in tissue engineering, drug delivery, and biosensing.