Biomimetic Dendritic Electrodes Tune The Neural Network Behavior and Communication

The interaction between electrogenic cells and external devices is indispensable for tasks like cell recording and stimulation. In particular, the physical cell- chip coupling has a crucial impact on the electrical conduction mechanism. A deepened comprehension of how cells interact with artificial materials is of utmost importance in the quest for effective interfaces. The process of cells adhering to and spreading on pseudo 3D micro-structures, is a well-coordinated mechanism that hinges on cell adhesion and the cell's capacity to adapt its cytoskeletal architecture to conform to vertically aligned structures[1, 2]. This scenario highlights a knowledge gap in our understanding of how to modulate neural network development and how cell membranes conform to protruding vertical electrodes, particularly for creating an effective 3D representation of the cleft to be integrated into the cell-electrode equivalent circuit for recording and stimulation modeling. On this purpose a biomimetic dendritic electrode[3] has been fabricated by using the two-photon polymerization lithography[4].<br/>Firstly, three structures’ geometry have been identified: thin that can initiate contacts with presynaptic terminals and are therefore essential in the initial stages of spinogenesis; the mushroom shape as a result of the plastic and dynamic reshaping of the neuronal circuits during synaptic development and the stubby. The experimental approach involved the primary cortical neurons. In our work, we’ve demonstrated the mechanical interactions occurring at focal adhesion sites. These interactions oversee the continuous remodeling and adjustment of cells on the material's surface and have the capacity to generate localized traction forces on the substrate. Neurons can utilize these forces to facilitate directed movement through contact guidance. Additionally, this mechanism promotes the engulfment event by facilitating membrane invagination, leading to the precise localization of transmembrane proteins, including integrins. This localization helps induce a specific cytoskeletal arrangement. Furthermore, our results indicate how microelectrodes can impact directionality and influence the remodeling of the neural network, particularly affecting the growth cone phase, shifting from pausing to a resting state. Importantly, we've demonstrated that the growth cone rate changes in response to different pitch configurations. Significantly, our research has revealed that biomimetic topographical cues can swiftly impact membrane adhesion proteins and enhance the efficiency, as demonstrated through the 3D reconstruction integrated into an electrical equivalent model. With an eye toward future applications in controlling signal dissipation, this work has the potential to enhance the recording of electrogenic cells.<br/><br/>1. Mariano A, Lubrano C, Bruno U, Ausilio C, Dinger NB, Santoro F (2021) Advances in Cell-Conductive Polymer Biointerfaces and Role of the Plasma Membrane. Chem Rev acs.chemrev.1c00363<br/>2. Santoro F, Zhao W, Joubert L-M, et al (2017) Revealing the Cell–Material Interface with Nanometer Resolution by Focused Ion Beam/Scanning Electron Microscopy. ACS Nano 11:8320–8328<br/>3. Mariano A, Bovio CL, Criscuolo V, Santoro F (2022) Bioinspired micro- and nano-structured neural interfaces. Nanotechnology 33:492501<br/>4. Harinarayana V, Shin YC (2021) Two-photon lithography for three-dimensional fabrication in micro/nanoscale regime: A comprehensive review. Optics & Laser Technology 142:107180<br/>5. A. Belu, J . Schnitker, S. Bertazzo, E. Neumann, D. Mayer, A. Offenhausser, Santoro F (2015) Ultra-thin resin embedding method for scanning electron microscopy of individual cells on high and low aspect ratio 3D nanostructures. Journal of Microscopy