arXiv subjects

Giovanni Di Muccio

Publications and source records attributed to Giovanni Di Muccio.

7 recordsLinked to original sources

arXiv2025

A nanopore-gated sub-attoliter silicon nanocavity for single-molecule trapping and analysis

Biomolecules exhibit dynamic conformations critical to their functions, yet observing these processes at the single-molecule level under native conditions remains a formidable challenge. While surface immobilization has been widely used to extend observation times, it could disrupt molecular dynamics and impede biological function. Moreover, the study of weak molecular interactions requires high local concentrations, often leading to problems with signal saturation in fluorescence-based approaches. Recent advancements in single-molecule trapping techniques have addressed some limitations, but achieving precise, controllable, long-term trapping in a molecularly crowded environment without external forces remains difficult. Here, we introduce a nanopore-gated sub-attoliter silicon nanocavity that enables precise, non-perturbative trapping of individual biomolecules for extended observation times, eliminating the need for external forces. Using nucleosomes as model systems, we demonstrate single-molecule Förster resonance energy transfer (smFRET) to monitor relative distances. Our data also show that an applied electric field can modulate the conformational properties of macromolecules, emphasizing a key advantage of our device: it does not require an electric field to retain trapped molecules. We envision this nanocavity platform as a powerful tool for interrogating molecular dynamics in physiologically relevant environments, offering unperturbed access to weak and transient interactions that are central to biological regulation.

physics.ins-det↗

arXiv2025

Electrodrying in nanopores: from fundamentals to iontronic and memristive applications

Iontronics is a burgeoning paradigm that employs ions in solution as information carriers for sensing and computing, e.g., in neuromorphic devices. The fundamentally different working principle as compared to electronics requires novel approaches and concepts to control the impedance of nanoscale fluidic circuit elements, such as nanopores. For instance, previous research has focused on voltage-induced pore wetting as a means to trigger conduction in nanopores. The present study explores the opposite counter-intuitive mechanism: using voltage to dry hydrophobic nanopores and, therefore, to turn off conduction. This "electrodrying" concept affords exquisite, bidirectional control over the conductance of nanopores additionally showing hysteresis in the current-voltage curve that is the fingerprint of memristors. Using an analytical model and free-energy molecular dynamics simulations, we explain the physical mechanism underlying electrodrying and provide clear design criteria for solid-state and biological nanopores with bidirectional control over conductance. The electrical behaviour of electrodrying nanopores shows two unique features: i) the hysteresis loop is shifted from the origin, accounting for the fifth, previously unreported memristor type and ii) negative differential resistance is observed over a broad voltage range in which the non-conductive state is favoured by electrodrying. These properties are demonstrated in a short-term memory task and in an iontronic oscillator circuit to showcase their potential in neuromorphic applications and iontronic devices. Finally, we validate our predictions through experiments on engineered dipolar hydrophobic CytK nanopores, whose voltage-dependent conductance substantiates the electrodrying concept.

physics.chem-ph↗

arXiv2024

Bubbles enable volumetric negative compressibility in metastable elastocapillary systems

Although coveted in applications, few materials expand when subject to compression or contract under decompression, i.e., exhibit the negative compressibility phenomenon. A key step to achieve such counterintuitive behaviour is the destabilisations of (meta)stable equilibria of the constituents. Here, we propose a simple strategy to obtain negative compressibility exploiting capillary forces both to precompress the elastic material and to release such precompression by a threshold phenomenon -- the reversible formation of a bubble in a lyophobic flexible cavity. We demonstrate that the solid part of such metastable elastocapillary systems displays negative compressibility across different scales: hydrophobic microporous materials, proteins, and millimetre-sized laminae. This concept is applicable to fields such as porous materials, biomolecules, sensors and may be easily extended to create unexpected material susceptibilities.

cond-mat.soft↗

arXiv2024

Lipid-mediated hydrophobic gating in the BK potassium channel

The large-conductance, calcium-activated potassium (BK) channel lacks the typical intracellular bundle-crossing gate present in most ion channels of the 6TM family. This observation, initially inferred from Ca$^{2+}$-free-pore accessibility experiments and recently corroborated by a CryoEM structure of the non-conductive state, raises a puzzling question: how can gating occur in absence of steric hindrance? To answer this question, we carried out molecular simulations and accurate free energy calculations to obtain a microscopic picture of the sequence of events that, starting from a Ca$^{2+}$-free state leads to ion conduction upon Ca$^{2+}$ binding. Our results highlight an unexpected role for annular lipids, which turn out to be an integral part of the gating machinery. Due to the presence of fenestrations, the "closed" Ca$^{2+}$-free pore can be occupied by the methyl groups from the lipid alkyl chains. This dynamic occupancy triggers and stabilizes the nucleation of a vapor bubble into the inner pore cavity, thus hindering ion conduction. By contrast, Ca$^{2+}$ binding results into a displacement of these lipids outside the inner cavity, lowering the hydrophobicity of this region and thus allowing for pore hydration and conduction. This lipid-mediated hydrophobic gating rationalizes several seemingly problematic experimental observations, including the state-dependent pore accessibility of blockers.

q-bio.BM↗

arXiv2023

Voltage controlled iontronic switches: a computational method to predict electrowetting in hydrophobically gated nanopores

Reliable and controllable switches are crucial in nanofluidics and iontronics. Ion channels in nature serve as a rich source of inspiration due to their intricate mechanisms modulated by stimuli like pressure, temperature, chemicals, and voltage. The artificial replication of the properties of these channels is challenging due to their complex chemistry, limited stability range, and intricate moving parts, allosterically modulated. Nonetheless, we can harness some of their gating mechanisms for nanofluidic and iontronic purposes. This theoretical and computational study explores the use of electrowetting in hydrophobic nanopores to control their conductance using an external applied voltage. We employ restrained molecular dynamics to calculate the free energy required for wetting a model nanopore under different voltages. Utilizing a simple theory, we generate free energy profiles across a wide voltage range. We also computed transition rates between conductive and non-conductive states, showing their voltage dependence and how this behaviour can impair memory to the system, resembling the memristor behaviour voltage-gated channels in the brain. These findings offer a promising avenue for designing and controlling hydrophobic nanopores via electrowetting, enabling potential applications in neuromorphic iontronics.

cond-mat.mes-hall↗

arXiv2022

Geometrically Induced Selectivity and Unidirectional Electroosmosis in Uncharged Nanopores

Selectivity towards positive and negative ions in nanopores is often associated with electroosmotic flow, the control of which is pivotal in several micro-nanofluidic technologies. Selectivity is traditionally understood to be a consequence of surface charges that alter the ion distribution in the pore lumen. Here we present a purely geometrical mechanism to induce ionic selectivity and electroosmotic flow in uncharged nanopores and we tested it via molecular dynamics simulations. Our approach exploits the accumulation of charges, driven by an external electric field, in a coaxial cavity that decorates the membrane close to the pore entrance. The selectivity was shown to depend on the applied voltage and results to be completely inverted when reverting the voltage. The simultaneous inversion of ionic selectivity and electric field direction causes a unidirectional electroosmotic flow. We developed a quantitatively accurate theoretical model for designing pore geometry to achieve the desired electroosmotic velocity. Finally, we demonstrate that unidirectional electroosmosis also occurs for a biological pore whose structure presents a coaxial cavity surrounding the pore constriction. The capability to induce ion selectivity without altering the pore lumen shape or the surface charge may open the way to a more flexible design of selective membranes.

physics.flu-dyn↗

arXiv2022

Electroosmosis in nanopores: Computational methods and technological applications

Electroosmosis is a fascinating effect where liquid motion is induced by an applied electric field. Counter ions accumulate in the vicinity of charged surfaces, triggering a coupling between liquid mass transport and external electric field. In nanofluidic technologies, where surfaces play an exacerbated role, electroosmosis is thus of primary importance. Its consequences on the transport properties in biological and synthetic nanopores are subtle and intricate. Thorough understanding is therefore challenging yet crucial to fully assess the mechanisms at play. Here, we review recent progress on computational techniques for the analysis of electroosmosis and discuss technological applications, in particular for sensing devices.

physics.flu-dyn↗