Physical Study of Cell Response to Remotely Vibrated Magnetic Nanoparticles in Mechano-Mimetic Environments
Place : IRIG/SPINTEC, CEA Building 10.05, auditorium 445 (presential access to the conference room at CEA in Grenoble requires an entry authorization, request it before January 20th to admin.spintec@cea.fr)
visio conference : https://univ-grenoble-alpes-fr.zoom.us/j/98769867024
Meeting ID: 987 6986 7024
Passcode: 025918
Abstract : Nanoparticles are reshaping the biomedical field thanks to their ability to be remotely controlled by external magnetic fields. Among established research topics such as hyperthermia, magnetic particle tracking or drug delivery, there is growing interest in studying the effects on cell fate of mechanical stresses exerted by magnetic nanoparticles resulting from the application of low-frequency fields. Micrometric disc-shaped particles are an optimal tool for these studies because of their high shape anisotropy, which enables magnetic torques to be converted efficiently into mechanical torques. These particles have shown promising in vitro results for the development of new therapies using mechanical actuation. Nevertheless, the now well established field of mechanobiology has highlighted the importance of the mechanical properties of the microenvironment in which cells live for all their functions. And traditional in vitro culture, based on the use of rigid plastic culture plates, fails to reproduce physiological phenotypes.
In this context, our aim is to study whether the interaction between cells and vortex discs is influenced by the mechanical properties of the surrounding matrix, both in the absence of field and when the particles are set in motion by a low-frequency rotating magnetic field. To do this, we explored the interaction of these particles with a standard cell line of human glioblastoma U87-MG and the effect of their magneto-induced vibration when grown in a biomimetic mechanical environment. This artificial environment consists of a flexible polyacrylamide culture substrate, which has recently been shown to bring cells to a biological state close to that of the human body. We first analysed the cytotoxic effect of nanoparticles as a function of the stiffness of the culture substrate, which represents, to our knowledge, the very first study of the mechanosensitivity of nanoparticle-induced toxicity. Our main finding is that the soft environment amplifies the severity of particle toxicity. We also demonstrated that the physical properties of the surrounding matrix determine the aftermaths of magneto-mechanical stimulation on cell fate.
Our results in this relevant in vitro model could not only provide more precise information on particle-induced cytotoxicity and the action of mechanical stimulation, but also accelerate progress in preclinical testing when considering mechanically-driven therapies with magnetic nanoparticles.
Keywords: Magnetic nanoparticles, mechanobiogy, cytoskeleton.
Jury :
- Jean-François Berret CNRS, research director, Laboratoire Matière et Système Complexes – Université Paris Cité, Rapporteur
- Véronique Gigoux, Chargee de recherche HDR CNRS, INSERM, Centre de Recherches en Cancérologie de Toulouse, Rapporteure
- Liliana Buda-Prejbeanu, Professeure des universités, Grenoble INP-UGA, Examinatrice
- Claire Wilhelm, research director CNRS, Institut Curie, Paris, Examinatrice
Thesis supervisors :
Alice Nicolas, research director CNRS, LTM Grenoble. Thesis director
Robert Morel, research director CEA, SPINTEC Grenoble. Thesis co-director