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Biology subjects

Piazzoni, C.

Publications and source records attributed to Piazzoni, C..

5 recordsLinked to original sources

Nanostructured Zirconia thin films as neurogliomorphic interface for neural cells of central and peripheral nervous system

Recent advances in neuroscience have highlighted the central role of glial cells, particularly astrocytes, in regulating neural network activity through calcium-dependent neuron-glia communication. In parallel, nanostructured cluster-assembled materials have emerged as promising candidates for developing brain-machine interfaces, because of their biomimetic morphology, mechanotransductive properties and neuromorphic behavior. Among these, nanostructured zirconium oxide (ns-ZrOx) thin films have recently demonstrated memristive and signal-processing capabilities compatible with biohybrid neural systems, yet their interaction with heterogeneous neuroglial networks remains poorly understood. Here, we investigate the biocompatibility and functional effects of ns-ZrOx interfaces on primary astrocytes and dorsal root ganglion (DRG) neuron-glia co-cultures, comparing nanostructured and flat zirconia substrates. Both substrates supported cellular adhesion, survival, and differentiation. However, ns-ZrOx selectively enhanced glial calcium signaling, increasing transient amplitude and accelerating response kinetics in both central and peripheral glial populations. Our findings identify ns-ZrOx as an active neurogliomorphic interface capable of modulating neuron-glia communication through nanoscale material properties. By bridging glial physiology with neuromorphic nanomaterials, this work supports the development of hybrid bioelectronic platforms integrating living neural networks with adaptive functional materials for brain-inspired computing and advanced neural interfaces.

bioengineering↗

The Interaction with Nanotopographical Environment regulates nuclear mechanoresponse in mESCs via Histone Demethylase KDM3A

Cell identity is traditionally viewed as a product of biochemical signalling, yet cells are exposed to defined physical landscapes, whose role in fate control remains unclear. In particular, how pluripotent stem cells integrate nanoscale extracellular cues into gene regulatory programs remains poorly understood. Here, we show that biomimetic substrate nanotopography acts as a potent regulator of naive pluripotency in mouse embryonic stem cells (mESCs). Using supersonic cluster beam deposition, we generate substrates with defined nanotopography that recapitulate native features of extracellular matrix. We demonstrate that nanotopography induces a mechanically relaxed cell state characterised by reduced adhesion, cellular and nuclear softening, and altered nuclear architecture. These mechanical changes are coupled with chromatin remodelling, including reduced H3K27me3 and H3K9me2, redistribution of H3K9me3, and increased H3K4me3. Transcriptomic analyses reveal suppression of adhesion- and cytoskeleton-associated programs together with the activation of a naive pluripotency transcriptional signature, including upregulation of Nanog. Mechanistically, we identify the H3K9 demethylase KDM3A as a mechanosensitive epigenetic regulator required for nanotopography-induced Nanog expression. Together, our findings uncover a novel mechanotransductive pathway directly linking extracellular nanotopography to chromatin state and pluripotency control.

molecular biology↗

The glycocalyx affects force loading-dependent mechanotransductive topography sensing at the nanoscale

The cell/microenvironment interface is the starting point of integrin-mediated mechanotransduction, but many details of mechanotransductive signal integration remain elusive due to the complexity of the involved (extra)cellular structures, such as the glycocalyx. We used nano-bio-interfaces reproducing the complex nanotopographical features of the extracellular matrix to analyse the glycocalyx impact on PC12 cell mechanosensing at the nanoscale (e.g., by force spectroscopy with functionalised probes). Our data demonstrates that the glycocalyx configuration affects spatio-temporal nanotopography-sensitive mechanotransductive events at the cell/microenvironment interface. Opposing effects of glycocalyx removal were observed, when comparing flat and specific nanotopographical conditions. The excessive retrograde actin flow speed and force loading are strongly reduced on certain nanotopographies upon removal of the native glycocalyx, while on the flat substrate we observe the opposite trend. Our results highlight the importance of the glycocalyx configuration in a molecular clutch force loading-dependent cellular mechanism for mechanosensing of microenvironmental nanotopographical features.

biophysics↗

Adhesion force spectroscopy with nanostructured colloidal probes reveals nanotopography-dependent early mechanotransductive interactions at the cell membrane level

Mechanosensing, the ability of cells to perceive and interpret the microenvironmental biophysical cues (such as the nanotopography), impacts strongly on cellular behaviour through mechanotransductive processes and signalling. These events are predominantly mediated by integrins, the principal cellular adhesion receptors located at the cell/extracellular matrix (ECM) interface. Because of the typical piconewton force range and nanometre length scale of mechanotransductive interactions, achieving a detailed understanding of the spatiotemporal dynamics occurring at the cell/microenvironment interface is challenging; sophisticated interdisciplinary methodologies are required. Moreover, an accurate control over the nanotopographical features of the microenvironment is essential, in order to systematically investigate and precisely assess the influence of the different nanotopographical motifs on the mechanotransductive process. In this framework, we were able to study and quantify the impact of microenvironmental nanotopography on early cellular adhesion events by means of adhesion force spectroscopy based on innovative colloidal probes mimicking the nanotopography of natural ECMs. These probes provided the opportunity to detect nanotopography-specific modulations of the molecular force loading dynamics and integrin clustering at the level of single binding events, in the critical time window of nascent adhesion formation. Following this approach, we found that the nanotopographical features are responsible for an excessive force loading in single adhesion sites after 20 - 60 s of interaction, causing a drop in the number of adhesion sites. However, by manganese treatment we demonstrated that the availability of activated integrins is a critical regulatory factor for these nanotopography-dependent dynamics.

biophysics↗

Neuronal Cells Confinement by Micropatterned Cluster-Assembled Dots with Mechanotransductive Nanotopography

The in vitro fabrication of neural networks able to simulate brain circuits and to maintain their native connectivity is of strategic importance to gain a deep understanding of neural circuit physiology and brain natural computational algorithm(s). This would also enable a wide-range of applications including the development of efficient brain-on-chip devices or brain-computer interfaces. Chemical and mechanotransductive cues cooperate to promote proper development and functioning of neural networks. Since the 80s, controlled growth of mammalian neuronal cells on micrometric patterned chemical cues with the development of synaptic connections and electrical activity has been reported, however the role of mechanotransductive signaling on the growth/organization of neural networks has not been investigated so far. Here we report the fabrication and characterization of patterned substrates for neuronal culture with a controlled structure both at the nano- and microscale suitable for the selective adhesion of neuronal cells. Nanostructured micrometric dots were patterned on passivated cell-repellent glass substrates by supersonic cluster beam deposition of zirconia nanoparticles through stencil masks. Cluster-assembled nanostructured zirconia surfaces are characterized by nanotopographical features that can direct the maturation of neural networks by mechanotransductive signaling. Our approach produces a controlled microscale pattern of adhesive areas with predetermined nanoscale morphology. We have validated these micropatterned substrates using a neuronal cell line (PC12 cells) and cultured hippocampal neurons. While cells have been uniformly plated on the substrates, they adhered only on the nanostructured zirconia regions, remaining effectively confined inside the nanostructured dots on which they were found to grow, move and differentiate.

bioengineering↗