Metal-organic frameworks as an active substrate for cell-interaction studies and cell-on-a-chip platforms

Metal-organic frameworks (MOFs) are an emerging class of nanomaterials with immense biomedical potential for their unique interactions with biological and organic materials. In this work, we select two candidate two-dimensional (2D) MOF systems based on Fe³⁺ and Ni²⁺ metal centers and 2-aminoterephthalate acid ligand (Fe-MOF and Ni-MOF) and evaluate their performance as an active interface for study of cell-interactions. 2D Fe-MOF and Ni-MOF were synthesized onto hydroxyl-modified gold and glass substrates using a layer-by-layer liquid-phase-epitaxy (LbL-LPE) growth at room temperature and used as active substrates (Fe-MOF/glass, Fe-MOF/Au, Ni-MOF/glass and Ni-MOF/Au, respectively) for MTT cell-proliferation and reactive oxygen species tests using the PC-12 cell-line in order to investigate the biocompatibility. Immunostaining and morphological analyses of PC-12 cells on MOF interfaces suggested a stronger cell-substrate interaction in comparison to glass and were further characterized using the Electrical Cell-substrate Impedance Sensing (ECIS) technique, here for the first time, employed to study cell attachment, spreading and proliferation on 2D Fe-MOF. The 2D Fe-MOF showed superior long-term stability in cell culture medium by recording impedance over 24 h, crucial to monitor cell-dynamics at a solid-liquid interface. A significant increase of interfacial impedance was observed in ECIS, due to PC-12 cells adhering onto 2D Fe-MOF, which was also confirmed by the focused ion beam etching followed by scanning electron microscopy. Our novel findings, therefore, suggest 2D MOFs as highly suitable platform for the study of cell-related interactions using electrical techniques and potentially pave the way for future use of MOFs for bioelectronics and biosensor applications.