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Remote control of cellular signalling triggered by magnetic switching

Project description

Magnetic fields work magic on nanoswitches and promote deep wound healing

In the past decade, increasing evidence has supported the role of integrated mechanical and chemical signalling networks in controlling cell activity and regulating wound repair. Harnessing mechanotransduction, the ways in which cells convert mechanical stimuli into electrochemical activity, is a growing area of research in skin repair. However, techniques are needed to turn non-invasive stimuli into cellular signals that are tightly controlled in space and time, so as to promote healing in deep tissues. The EU-funded SIROCCO project is exploiting 'magnetic switches' to get the job done. Functionalised magnetic nanoparticles will recognise cells of interest and attach to the cell membrane surface. Once attached, they will be activated by magnetic fields, inducing intracellular signalling pathways to enhance wound healing, and potentially even modulate stem cell fate. These magnetic nanoswitches could be exploited in many other pathways and disease processes in future.

Objective

It is becoming increasingly clear that successful tissue engineering rests on capitalizing on more comprehensive understanding of mechanotransduction and its implication in skin homeostasis. 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 activation 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 switchers in order to enhance wound healing. Magnetic nanoparticles functionalized with oriented fragments of proteins will selectively recognize cell surface adhesion receptors (cadherins) present on the membrane of living cells. Once attached to the cellular surface, the MNPs will be activated using external magnetic fields in order to control key intracellular pathways. This ambitious goal will be validated using genetically modified 2D and 3D in vitro models, and the possibility to enhance wound healing and to modulate stem cell fate will be tested. High precision remote control of cellular functions with temporal resolution is an extremely hot topic in tissue engineering. SIROCCO will go well beyond current state-of-the-art for non-invasive actuation of cellular functions in situ and will provide a powerful magnetomechanical transduction tool for mechanotransduction and tissue regeneration. The fundamental scientific advances proposed by SIROCCO are cross-disciplinary since these magnetic nanoswitchers may also find widespread applications in other processes where these pathways are involved, for instance in tumour progression.

Host institution

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Net EU contribution
€ 1 798 454,00
Address
CALLE SERRANO 117
28006 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
Links
Total cost
€ 1 798 454,00

Beneficiaries (1)