NanoForceX

Mechanosensitive fluorescent Nanoparticles to sense Forces in the eXtracellular space of multicellular assemblies

NanoForceX is a two years international ANR led by Chloé Grazon (LCPO, U. Bordeaux, Fr) and Jessica Clough (Adolphe Merkel Institute, Fribourg, Switzerland) in collaboration with Morgane Rosendale (IINS, U. Bordeaux, Fr)

Project summary:
Cells are exquisitely equipped to sense forces within tissues in a way that influences their behaviour. Developing tools to detect and quantify these forces is thus critical for understanding the cellular mechanisms at play in physiology (cell migration, proliferation…) and pathology (developmental disorders, cancer…). To date, mechano-sensors reporting on cellular forces come in two flavours: genetically encodable proteins to sense intracellular forces and engineered molecular tools to sense extracellular forces. While the former can be expressed in a variety of biological sample preparations, the non-encodable nature of the latter has limited its use to simplified systems, typically consisting of isolated cells on a glass surface. The complexity and variability of soft, dense, 3-dimensional biological tissues are thus all, but lost. The aim of the NanoForceX project is thus to develop nanometric mechano-sensors capable of detecting molecular tension in the extracellular space of multicellular assemblies. To this aim, we propose two biocompatible mechano-sensing platforms for reversible, high signal-to-noise, pN to nN for force measurements at the nanoscale. Both are based on core-shell polymeric nanoparticles targeted to transmembrane receptors responsible for cellular adhesion. The first will consist of existing dye-labelled elastic peptides grafted onto fluorescent particles to report on tension via ratiometric FRET. The second will make use of mechano-sensitive chemical groups currently used for mechano-sensing in polymers. Grafted onto nanoparticles, these so-called mechanophores will report on tension via fluorogenic bond rearrangements. Our consortium ideally combines the synergistic expertise of C. Grazon (FR) in fluorescent nanoparticle synthesis and functionalisation, J. Clough (CH) in mechanophore synthesis and characterisation, and M. Rosendale (FR) in biosensing and bioimaging to address key fundamental and technological challenges in mechanobiology.

Funding: ANR-25-CE06-1059-01