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Understanding cell-nanoparticle interactions through mechanobiology

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.

Call for proposal

H2020-MSCA-IF-2020
See other projects for this call

Funding Scheme

MSCA-IF-GF - Global Fellowships

Coordinator

FAKULTNI NEMOCNICE U SV. ANNY V BRNE
Address
Pekarska 53
656 91 Brno
Czechia
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 243 963,60

Partners (1)

UNIVERSITY OF MELBOURNE
Australia
Address
Parkvilleoffice Of The Vice Chancellor
3010 Melbourne
Activity type
Higher or Secondary Education Establishments