Czech Republic Project Notice - Understanding Cell-Nanoparticle Interactions Through Mechanobiology


Project Notice

PNR 50519
Project Name Understanding cell-nanoparticle interactions through mechanobiology
Project Detail Mechanobiology of cell–nanoparticle interactions The successful clinical translation of nanoparticle-based therapies requires a better understanding of the mechanobiology of cell–nanoparticle interactions to overcome inefficient targeting. Mechanosensing is the ability of cells to sense mechanical cues from their microenvironment that affect the expression of genes involved in the cells’ migration, survival and resistance to drugs. The Hippo signalling pathway controls cell proliferation and apoptosis, and represents an excellent mechanobiology model as it is involved in pathological diseases and tissue regeneration. Funded by the Marie Sklodowska-Curie Actions programme, the MecHA-Nano project aims to study the details of the response of the Hippo pathway upon cell interaction with nanoparticles, paving the way for nanoparticle application as a tune-up tool of mechanosensing. The clinical translation of nanoparticle-based therapies over the last decade has been hampered by issues such as inefficient targeting and limited therapeutic effect. This poor translational outcome calls for deeper understanding of the biomechanics of cell-nanoparticle (cell-NP) interactions. Indeed, targeting mechanosensing-activated cell pathways is suitable for tuning cell fate and readdressing its functions, as mechanosensing components control the expression of genes involved in the cell’s migration, survival and resistance to drugs. Hippo pathway appears to be one of the most promising mechanobiology pathway, as it is involved in pathological diseases and tissue regeneration. This project aims to address the response of this pathway on cells upon interaction with nanoparticles. Indeed, tuning cell mechanosensing with nanoparticles is likely to hold great potentiality to control cell functionalities. The first objective will be the synthesis of nanoparticles of different size, shape and stiffness, using a silica scaffold coated with hyaluronic acid via metal-phenolic network assembly with exceptional physicochemical properties. The second objective consists in the application of Superresolution microscopy for studying cell-NP interactions with unprecedented detail and unveil the interaction/structure/ spatiotemporal localization of mechanosensing components related to the Hippo pathway (i.e. YAP, actin and focal adhesions) at molecular level. The third objective will be the deep analysis of the molecular biology and biochemistry of mechanosensing proteins (i.e. YAP, TAZ, RhoA and Rock), and their downstream effectors (i.e. TEAD and transcriptional factors) involved in the response to cell-NP interaction. The forth objective will pursue the analysis of these interactions using NenoVision technology (LiteScope), for measuring cell stiffness at the boundary of cell-NP contact with unique resolution.
Funded By Self-Funded
Country Czech Republic , Eastern Europe
Project Value CZK 243,964

Contact Information

Company Name FAKULTNI NEMOCNICE U SV. ANNY V BRNE
Web Site https://cordis.europa.eu/project/id/101031744

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