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Understanding cell-nanoparticle interactions through mechanobiology

Project description

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 Skłodowska-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.

Objective

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.

Coordinator

FAKULTNI NEMOCNICE U SV ANNY V BRNE
Net EU contribution
€ 243 963,60
Address
PEKARSKA 53
602 00 Brno
Czechia

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Region
Česko Jihovýchod Jihomoravský kraj
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 243 963,60

Partners (1)