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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 physiological in vivo ECM-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.

SUBMITTER: Schulte C

PROVIDER: S-EPMC5114288 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Scale Invariant Disordered Nanotopography Promotes Hippocampal Neuron Development and Maturation with Involvement of Mechanotransductive Pathways.

Schulte Carsten C Ripamonti Maddalena M Maffioli Elisa E Cappelluti Martino A MA Nonnis Simona S Puricelli Luca L Lamanna Jacopo J Piazzoni Claudio C Podestà Alessandro A Lenardi Cristina C Tedeschi Gabriella G Malgaroli Antonio A Milani Paolo P

Frontiers in cellular neuroscience 20161118

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 nanotopogr ...[more]

PMID: 27917111

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Project description:Neuronal cells are competent in precisely sensing nanotopographical features of their microenvironment. The perceived microenvironmental information will be "interpreted" by mechanotransductive processes and impacts on neuronal functioning and differentiation. Attempts to influence neuronal differentiation by engineering substrates that mimic appropriate extracellular matrix (ECM) topographies are hampered by the fact that profound details of mechanosensing/-transduction complexity remain elusive. Introducing omics methods into these biomaterial approaches has the potential to provide a deeper insight into the molecular processes and signaling cascades underlying mechanosensing/-transduction but their exigence in cellular material is often opposed by technical limitations of major substrate top-down fabrication methods. Supersonic cluster beam deposition (SCBD) allows instead the bottom-up fabrication of nanostructured substrates over large areas characterized by a quantitatively controllable ECM-like nanoroughness that has been recently shown to foster neuron differentiation and maturation. Exploiting this capacity of SCBD, we challenged mechanosensing/-transduction and differentiative behavior of neuron-like PC12 cells with diverse nanotopographies and/or changes of their biomechanical status, and analyzed their phosphoproteomic profiles in these settings. Versatile proteins that can be associated to significant processes along the mechanotransductive signal sequence, i.e., cell/cell interaction, glycocalyx and ECM, membrane/f-actin linkage and integrin activation, cell/substrate interaction, integrin adhesion complex, actomyosin organization/cellular mechanics, nuclear organization, and transcriptional regulation, were affected. The phosphoproteomic data suggested furthermore an involvement of ILK, mTOR, Wnt, and calcium signaling in these nanotopography- and/or cell mechanics-related processes. Altogether, potential nanotopography-sensitive mechanotransductive signaling hubs participating in neuronal differentiation were dissected.

Project description:Neuronal cells are competent in precisely sensing nanotopographical features of their microenvironment and the intrinsic information impacts on neuronal functioning and differentiation “interpreted” by mechanotransductive processes. Attempts to influence and direct neuronal differentiation behaviour by engineering substrates that mimic appropriate extracellular matrix (ECM) topographies are hampered by the difficulty since many details of mechanosensing/-transduction are still elusive. Introducing omics methods into these biomaterial approaches has the potential to provide a deeper insight into the molecular processes and signalling cascades underlying mechanosensing/-transduction but their exigence in cellular material is often opposed by technical limitations of the biomaterial fabrication methods. Supersonic cluster beam deposition (SCBD) of zirconia nanoparticles allows instead the realisation of large macroscopic areas with biocompatible nanostructured films equipped with controllable and reproducible ECM-like nanoroughness that have been recently shown to foster neuron differentiation and maturation. Exploiting this capacity of SCBD, we challenged mechanosensing/-transduction and differentiative behaviour of neuron-like PC12 cells interacting with diverse nanotopographies and/or by changing their biomechanical status, to analyse their phosphoproteomic profiles in these settings. Versatile proteins were found to be affected that can be associated to significant processes along the mechanotransductive signal sequence, i.e. cell/cell interaction, glycocalyx and ECM, membrane/f-actin linkage and integrin activation, cell/substrate interaction, IAC, actomyosin organisation/cellular mechanics, nuclear organisation and transcription. The phosphoproteomic data suggested furthermore an involvement of ILK, mTor, Wnt and calcium signalling in these nanotopography- and/or cell mechanics-related processes. Altogether, potential nanotopography-sensitive, mechanotransductive signalling hubs participating to neuronal differentiation were dissected.

Dataset Information

Scale Invariant Disordered Nanotopography Promotes Hippocampal Neuron Development and Maturation with Involvement of Mechanotransductive Pathways.

Publications

Scale Invariant Disordered Nanotopography Promotes Hippocampal Neuron Development and Maturation with Involvement of Mechanotransductive Pathways.

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