Remote control of cellular signalling triggered by magnetic switching

Información del proyecto

SIROCCO

Identificador del acuerdo de subvención: 853468

DOI

10.3030/853468

Proyecto cerrado

Fecha de la firma de la CE 20 Diciembre 2019

Fecha de inicio 1 Mayo 2020

Fecha de finalización 30 Abril 2026

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 1 798 454,00

Aportación de la UE

€ 1 798 454,00

Coordinado por

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain

Periodic Reporting for period 3 - SIROCCO (Remote control of cellular signalling triggered by magnetic switching)

Período documentado: 2023-05-01 hasta 2024-10-31

Resumen del contexto y de los objetivos generales del proyecto

It is becoming increasingly clear that successful tissue engineering rests on capitalizing on more comprehensive understanding of mechanotransduction. In fact, the study of mechanotransduction is now a burgeoning research field, helping us to understand how cells respond to mechanical stimuli and convert them into biochemical signals, which in turn sheds light on the remote control of intracellular functions and the treatment of diseases. However, external manipulation of cellular signalling constitutes an important challenge due to the lack of non-invasive techniques that can be tuned in a spatiotemporal manner at a deep-tissue level. SIROCCO aims to control different pathways related with cutaneous mechanotransduction by using magnetic nanoparticles in order to enhance wound healing. External magnetic fields will be applied to magnetic nanoparticles selectively attached to the membrane of living cells in order to create a force that can activate key intracellular pathways connected with mechanotransduction. Using genetically modified 2D and 3D in vitro models, the possibility to activate important pathways in order to enhance wound healing will be tested.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

We have synthesized magnetic nanoparticles (MNPs) of different sizes and compositions. We have then produced small protein fragments and attached them to the MNPs so that they can recognize the cell membrane in a specific way. We have studied the colocalization of MNPs with the cell membrane using cells expressing fluorescent proteins. To assess if we are activating key intracellular pathways, we have generated different reporter cell lines that turn fluorescent upon the activation of the pathways. We have also developed the first prototype to deliver magnetic cues to the cells.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

In order to target cell membranes, we optimized the bioconjugation of the proteins to MNPs using a rather novel alternative for orienting protein fragments on MNPs.
We expect to assess the activation of two important pathways by the end of the project.