Magnetic nanoparticles (MNPs) are widely studied in nanomedicine due to their attractive characteristics, such as their size comparable to biomolecules or their capacity to be detected and manipulated by remote magnetic fields, being able to generate responses like heat or tractional forces. A remote magnetic stimulation of the particles could be converted in a pulling force able to act directly on a cell membrane level if the particles are linked to it. Thus, MNPs can be used as magneto-mechanical activation platforms able to trigger cell responses in a controlled way if are targeted to mechanoreceptors, which can convert mechanical stimuli into biochemical signals (mechanotransduction).¹ In this context, mechanotransduction can take place in the adherent junctions, which rely on the role of E-cadherin. In fact, E-cadherin mechanotransduction is critical to mediate collective epithelial remodelling that takes place during tissue repair. Functionalizing MNPs with cadherins would allow to attach the nanomaterials to cell membranes, prior to an external magnetic stimulation that could be used to activate intracellular pathways implicated in regeneration processes. 

In the present work, cadherin fragments modified with a histidine-tag were attached on an oriented way to 13-nm iron oxide MNPs doped with manganese. To do so, MNPs were grafted with polyethylene glycol (PEG) chains and functionalized with a nitrilotriacetic acid derivative (LysNTA), a molecule able to chelate metal ions like Ni²⁺ or Co²⁺ used to bind histidine-tagged proteins. Then, the resulting functionalized MNPs were succesfully bioconjugated with cadherin fragments, showing the possibility to control the number of proteins/MNP and at the same time, the orientation of protein bioconjugation on the MNPs surface. Functionality of cadherin fragments attached on the MNPs surface was tested in bioconjugates with a high or low cadherin density by an aggregation assay in presence or absence of calcium ions (PBS or dPBS), since cadherins are well folded and active only in presence of calcium, promoting the aggregation only on the bioconjugates with a high cadherin density. Besides, bioconjugates with high or low cadherin density were incubated with cell cultures positive and negative for cadherin expression, after incubation high cadherin density bioconjugates were observed in higher quantity compared with low cadherin density and the biconjugates were present only in positive-cadherin cells.