Magnetic Nanoparticles Coupled to Cadherins as Smart Materials to Activate Mechanoreceptors and Intracellular Pathways

Magnetic particles are stimuli-responsive materials, that coupled to magnetic fields can be used as a tool to precisely manipulate mechanoreceptors by converting mechanical cues into biochemical signals. Compared to other techniques, the use of magnetic fields offers some advantages such as deep-tissue penetration, the possibility to apply a wide range of stresses and forces (fN to nN) without damaging the sample and the possibility to manipulate the receptors in a remote fashion.<br/>Although magnetic microparticles are widely used for this purpose, their large size might result in multivalent binding, causing clustering of receptors and activation of intracellular signalling even in the absence of a magnetic field. Alternatively, smaller magnetic nanoparticles (MNPs) offer undeniable advantages for manipulating mechanoreceptors as they show spatial control at the molecular level. However, MNPs exert smaller forces (in the range of fN or pN), that might be low to activate a mechanoreceptor. Therefore, a full optimization of the magnetic properties of the MNPs (through control of their size, shape and composition) and a correct design of the magnetic field applicator are crucial to reach this threshold.<br/>Cadherin fragments immobilized on magnetic nanoparticles can be used to selectively target cadherin expressing cells and to activate intracellular pathways if the fragments are correctly oriented on the nanoparticle surface. Critical factors that can ultimately affect cellular recognition are the orientation and density of the biomolecule on the MNP surface as the interaction between two E-cadherins depends on a correct spatial position. We will discuss how MNPs attached to cellular cadherins can be used to selectively stimulate important intracellular pathways related to cellular proliferation and the advantages of using these smart materials