Remote control of cellular signalling triggered by magnetic switching

ongoing

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.