It has become evident that physical stimuli of the cellular microenvironment transmit mechanical cues regulating key cellular functions, such as proliferation, migration, and malignant transformation. Accumulating evidence suggests that tumor cells face variable mechanical stimuli that may induce metabolic rewiring of tumor cells. However, the knowledge of how tumor cells adapt metabolism to external mechanical cues is still limited. We therefore designed soft 3D collagen scaffolds mimicking a pathological mechanical environment to decipher how liver tumor cells would adapt their metabolic activity to physical stimuli of the cellular microenvironment. Here, we report that the soft 3D microenvironment upregulates the glycolysis of HepG2 and Alexander cells. Both cell lines adapt their mitochondrial activity and function under growth in the soft 3D microenvironment. Cells grown in the soft 3D microenvironment exhibit marked mitochondrial depolarization, downregulation of mitochondrially encoded cytochrome c oxidase I, and slow proliferation rate in comparison with stiff monolayer cultures. Our data reveal the coupling of liver tumor glycolysis to mechanical cues. It is proposed here that soft 3D collagen scaffolds can serve as a useful model for future studies of mechanically regulated cellular functions of various liver (potentially other tissues as well) tumor cells.

• Klíčová slova
• cancer, cell plasticity, cytoskeleton, engineered cell microenvironments, extracellular matrix, mechanical forces, mitochondria,
• MeSH
• kolagen MeSH
• lidé MeSH
• mitochondriální dynamika MeSH
• nádorové mikroprostředí * MeSH
• nádory jater * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kolagen MeSH

DNA nanostructures (DNs) can be designed in a controlled and programmable manner, and these structures are increasingly used in a variety of biomedical applications, such as the delivery of therapeutic agents. When exposed to biological liquids, most nanomaterials become covered by a protein corona, which in turn modulates their cellular uptake and the biological response they elicit. However, the interplay between living cells and designed DNs are still not well established. Namely, there are very limited studies that assess protein corona impact on DN biological activity. Here, we analyzed the uptake of functionalized DNs in three distinct hepatic cell lines. Our analysis indicates that cellular uptake is linearly dependent on the cell size. Further, we show that the protein corona determines the endolysosomal vesicle escape efficiency of DNs coated with an endosome escape peptide. Our study offers an important basis for future optimization of DNs as delivery systems for various biomedical applications.

• Klíčová slova
• DNA nanotechnology, bionano interactions, cellular uptake, endolysosomal escape, nanotechnology, protein corona,
• MeSH
• adsorpce MeSH
• DNA chemie   metabolismus   MeSH
• endozomy metabolismus   MeSH
• kationické antimikrobiální peptidy chemie   metabolismus   MeSH
• konformace nukleové kyseliny MeSH
• lidé MeSH
• lyzozomy metabolismus   MeSH
• nádorové buněčné linie MeSH
• nanostruktury chemie   MeSH
• proteinová korona chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aurein 1.2 peptide MeSH Prohlížeč
• DNA MeSH
• kationické antimikrobiální peptidy MeSH
• proteinová korona MeSH