title: Scale Invariant Disordered Nanotopography Promotes Hippocampal Neuron Development and Maturation with Involvement of Mechanotransductive Pathways.
abstract: The identification of biomaterials which promote neuronal maturation up to the generation of integrated neural circuits is fundamental for modern neuroscience. The development of neural circuits arises from complex maturative processes regulated by poorly understood signaling events, often guided by the extracellular matrix (ECM). Here we report that nanostructured zirconia surfaces, produced by supersonic cluster beam deposition of zirconia nanoparticles and characterized by ECM-like nanotopographical features, can direct the maturation of neural networks. Hippocampal neurons cultured on such cluster-assembled surfaces displayed enhanced differentiation paralleled by functional changes. The latter was demonstrated by single-cell electrophysiology showing earlier action potential generation and increased spontaneous postsynaptic currents compared to the neurons grown on the featureless unnaturally flat standard control surfaces. Label-free shotgun proteomics broadly confirmed the functional changes and suggests furthermore a vast impact of the neuron/nanotopography interaction on mechanotransductive machinery components, known to control physiologicalin vivoECM-regulated axon guidance and synaptic plasticity. Our results indicate a potential of cluster-assembled zirconia nanotopography exploitable for the creation of efficient neural tissue interfaces and cell culture devices promoting neurogenic events, but also for unveiling mechanotransductive aspects of neuronal development and maturation.
authors.affiliation: Dipartimento di Fisica, Centro Interdisciplinare Materiali e Interfacce Nanostrutturate, Università degli Studi di MilanoMilan, Italy; Fondazione FilareteMilan, Italy.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schulte
authors.affiliation: Neurobiology of Learning Unit, Division of Neuroscience, Scientific Institute San Raffaele, Università Vita-Salute San Raffaele Milan, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Ripamonti
authors.affiliation: Fondazione FilareteMilan, Italy; Dipartimento di Medicina Veterinaria, Università degli Studi di MilanoMilan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Maffioli
authors.affiliation: Fondazione FilareteMilan, Italy; SEMM - European School of Molecular MedicineMilan, Italy.
authors.forename: Martino A
authors.initials: MA
authors.lastname: Cappelluti
authors.affiliation: Dipartimento di Medicina Veterinaria, Università degli Studi di Milano Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Nonnis
authors.affiliation: Dipartimento di Fisica, Centro Interdisciplinare Materiali e Interfacce Nanostrutturate, Università degli Studi di Milano Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Puricelli
authors.affiliation: Neurobiology of Learning Unit, Division of Neuroscience, Scientific Institute San Raffaele, Università Vita-Salute San Raffaele Milan, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Lamanna
authors.affiliation: Dipartimento di Fisica, Centro Interdisciplinare Materiali e Interfacce Nanostrutturate, Università degli Studi di Milano Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Piazzoni
authors.affiliation: Dipartimento di Fisica, Centro Interdisciplinare Materiali e Interfacce Nanostrutturate, Università degli Studi di Milano Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Podestà
authors.affiliation: Dipartimento di Fisica, Centro Interdisciplinare Materiali e Interfacce Nanostrutturate, Università degli Studi di Milano Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lenardi
authors.affiliation: Fondazione FilareteMilan, Italy; Dipartimento di Medicina Veterinaria, Università degli Studi di MilanoMilan, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Tedeschi
authors.affiliation: Neurobiology of Learning Unit, Division of Neuroscience, Scientific Institute San Raffaele, Università Vita-Salute San Raffaele Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Malgaroli
authors.affiliation: Dipartimento di Fisica, Centro Interdisciplinare Materiali e Interfacce Nanostrutturate, Università degli Studi di Milano Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Milani
keywords: biomaterial; integrin adhesion complex; mechanotransduction; neuronal cell adhesion molecules; neuronal differentiation; neuronal network maturation; proteomics; synaptic activity