Classical nucleation of vapor between hydrophobic plates.

In this work, an extended classical nucleation theory (CNT), including line tension, is used to disentangle classical and non-classical effects in the nucleation of vapor from a liquid confined between two hydrophobic plates at a nanometer distance. The proposed approach allowed us to gauge, from the available simulation work, the importance of elusive nanoscale effects, such as line tension and non-classical modifications of the nucleation mechanism. Surprisingly, the purely macroscopic theory is found to be in quantitative accord with the microscopic data, even for plate distances as small as 2 nm, whereas in extreme confinement (<1.5 nm), the CNT approximations proved to be unsatisfactory. These results suggest how classical nucleation theory still offers a computationally inexpensive and predictive tool useful in all domains where nanoconfined evaporation occurs-including nanotechnology, surface science, and biology.

Giant Negative Compressibility by Liquid Intrusion into Superhydrophobic Flexible Nanoporous Frameworks.

Materials or systems demonstrating negative linear compressibility (NLC), whose size increases (decreases) in at least one of their dimensions upon compression (decompression) are very rare. Materials demonstrating this effect in all their dimensions, negative volumetric compressibility (NVC), are exceptional. Here, by liquid porosimetry and in situ neutron diffraction, we show that one can achieve exceptional NLC and NVC values by nonwetting liquid intrusion in flexible porous media, namely in the ZIF-8 metal-organic framework (MOF). Atomistic simulations show that the volumetric expansion is due to the presence of liquid in the windows connecting the cavities of ZIF-8. This discovery paves the way for designing novel materials with exceptional NLC and NVC at reasonable pressures suitable for a wide range of applications.

Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons.

Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are clinically diagnosed using neuropsychological and cognitive tests, expensive neuroimaging-based approaches (MRI and PET) and invasive and time-consuming lumbar puncture for cerebrospinal fluid (CSF) sample collection to detect biomarkers. Thus, a rapid, simple and cost-effective approach to more easily access fluids and tissues is in great need. Here, we exploit the chemical direct reprogramming of patient skin fibroblasts into neurons (chemically induced neurons, ciNs) as a novel strategy for the rapid detection of different pathological markers of neurodegenerative diseases. We found that FAD fibroblasts have a reduced efficiency of reprogramming, and converted ciNs show a less complex neuronal network. In addition, ciNs from patients show misfolded protein accumulation and mitochondria ultrastructural abnormalities, biomarkers commonly associated with neurodegeneration. Moreover, for the first time, we show that microfluidic technology, in combination with chemical reprogramming, enables on-chip examination of disease pathological processes and may have important applications in diagnosis. In conclusion, ciNs on microfluidic devices represent a small-scale, non-invasive and cost-effective high-throughput tool for protein misfolding disease diagnosis and may be useful for new biomarker discovery, disease mechanism studies and design of personalised therapies.

Intrusion and extrusion of water in hydrophobic nanopores.

Heterogeneous systems composed of hydrophobic nanoporous materials and water are capable, depending on their characteristics, of efficiently dissipating (dampers) or storing ("molecular springs") energy. However, it is difficult to predict their properties based on macroscopic theories-classical capillarity for intrusion and classical nucleation theory (CNT) for extrusion-because of the peculiar behavior of water in extreme confinement. Here we use advanced molecular dynamics techniques to shed light on these nonclassical effects, which are often difficult to investigate directly via experiments, owing to the reduced dimensions of the pores. The string method in collective variables is used to simulate, without artifacts, the microscopic mechanism of water intrusion and extrusion in the pores, which are thermally activated, rare events. Simulations reveal three important nonclassical effects: the nucleation free-energy barriers are reduced eightfold compared with CNT, the intrusion pressure is increased due to nanoscale confinement, and the intrusion/extrusion hysteresis is practically suppressed for pores with diameters below 1.2 nm. The frequency and size dependence of hysteresis exposed by the present simulations explains several experimental results on nanoporous materials. Understanding physical phenomena peculiar to nanoconfined water paves the way for a better design of nanoporous materials for energy applications; for instance, by decreasing the size of the nanopores alone, it is possible to change their behavior from dampers to molecular springs.

The detailed acoustic signature of a micro-confined cavitation bubble.

Numerous scenarios exist for a cavitation bubble growing in a liquid. We focus here on cavitation phenomena within water under static tension in a confined environment. Drawing inspiration from the natural materials in plants, we design a novel experimental setup where a micrometric volume of water is confined by a hydrogel-based material. We show that, submerging the sample in a hypertonic solution, the water within the cavity is placed under tension and the acoustic emission produced by the resulting bubble nucleation is precisely detected. This new experimental procedure is able to strongly reduce the acoustic reflections occurring at the hydrogel/air interface with more classical techniques. We also propose a mathematical model to characterise the pressure wave emitted in order to correctly take into account the dissipation effect induced by the visco-elastic behaviour of the confining hydrogel. Both bubble resonant frequency and damping are captured by the model and quantitatively match the values found in the experiments.

Vapor nucleation paths in lyophobic nanopores.

In recent years, technologies revolving around the use of lyophobic nanopores gained considerable attention in both fundamental and applied research. Owing to the enormous internal surface area, heterogeneous lyophobic systems (HLS), constituted by a nanoporous lyophobic material and a non-wetting liquid, are promising candidates for the efficient storage or dissipation of mechanical energy. These diverse applications both rely on the forced intrusion and extrusion of the non-wetting liquid inside the pores; the behavior of HLS for storage or dissipation depends on the hysteresis between these two processes, which, in turn, are determined by the microscopic details of the system. It is easy to understand that molecular simulations provide an unmatched tool for understanding phenomena at these scales. In this contribution we use advanced atomistic simulation techniques in order to study the nucleation of vapor bubbles inside lyophobic mesopores. The use of the string method in collective variables allows us to overcome the computational challenges associated with the activated nature of the phenomenon, rendering a detailed picture of nucleation in confinement. In particular, this rare event method efficiently searches for the most probable nucleation path(s) in otherwise intractable, high-dimensional free-energy landscapes. Results reveal the existence of several independent nucleation paths associated with different free-energy barriers. In particular, there is a family of asymmetric transition paths, in which a bubble forms at one of the walls; the other family involves the formation of axisymmetric bubbles with an annulus shape. The computed free-energy profiles reveal that the asymmetric path is significantly more probable than the symmetric one, while the exact position where the asymmetric bubble forms is less relevant for the free energetics of the process. A comparison of the atomistic results with continuum models is also presented, showing how, for simple liquids in mesoporous materials of characteristic size of ca. 4nm, the nanoscale effects reported for smaller pores have a minor role. The atomistic estimates for the nucleation free-energy barrier are in qualitative accord with those that can be obtained using a macroscopic, capillary-based nucleation theory.

Wetting and cavitation pathways on nanodecorated surfaces.

In this contribution we study the wetting and nucleation of vapor bubbles on nanodecorated surfaces via free energy molecular dynamics simulations. The results shed light on the stability of superhydrophobicity in submerged surfaces with nanoscale corrugations. The re-entrant geometry of the cavities under investigation is capable of sustaining a confined vapor phase within the surface roughness (Cassie state) both for hydrophobic and hydrophilic combinations of liquid and solid. The atomistic system is of nanometric size; on this scale thermally activated events can play an important role ultimately determining the lifetime of the Cassie state. Such a superhydrophobic state can break down by full wetting of the texture at large pressures (Cassie-Wenzel transition) or by nucleating a vapor bubble at negative pressures (cavitation). Specialized rare event techniques show that several pathways for wetting and cavitation are possible, due to the complex surface geometry. The related free energy barriers are of the order of 100kBT and vary with pressure. The atomistic results are found to be in semi-quantitative accord with macroscopic capillarity theory. However, the latter is not capable of capturing the density fluctuations, which determine the destabilization of the confined liquid phase at negative pressures (liquid spinodal).

Focus Article: Theoretical aspects of vapor/gas nucleation at structured surfaces.

Heterogeneous nucleation is the preferential means of formation of a new phase. Gas and vapor nucleation in fluids under confinement or at textured surfaces is central for many phenomena of technological relevance, such as bubble release, cavitation, and biological growth. Understanding and developing quantitative models for nucleation is the key to control how bubbles are formed and to exploit them in technological applications. An example is the in silico design of textured surfaces or particles with tailored nucleation properties. However, despite the fact that gas/vapor nucleation has been investigated for more than one century, many aspects still remain unclear and a quantitative theory is still lacking; this is especially true for heterogeneous systems with nanoscale corrugations, for which experiments are difficult. The objective of this focus article is analyzing the main results of the last 10-20 years in the field, selecting few representative works out of this impressive body of the literature, and highlighting the open theoretical questions. We start by introducing classical theories of nucleation in homogeneous and in simple heterogeneous systems and then discuss their extension to complex heterogeneous cases. Then we describe results from recent theories and computer simulations aimed at overcoming the limitations of the simpler theories by considering explicitly the diffuse nature of the interfaces, atomistic, kinetic, and inertial effects.

Mechanism of the Cassie-Wenzel transition via the atomistic and continuum string methods.

The string method is a general and flexible strategy to compute the most probable transition path for an activated process (rare event). We apply here the atomistic string method in the density field to the Cassie-Wenzel transition, a central problem in the field of superhydrophobicity. We discuss in detail the mechanism of wetting of a submerged hydrophobic cavity of nanometer size and its dependence on the geometry of the cavity. Furthermore, we analyze the algorithmic analogies between the continuum "interface" string method and CREaM [Giacomello et al., Phys. Rev. Lett. 109, 226102 (2012)], a method inspired by the string that allows for a faster and simpler computation of the mechanism and of the free-energy profiles of the wetting process.

Relaxation of a steep density gradient in a simple fluid: comparison between atomistic and continuum modeling.

We compare dynamical nonequilibrium molecular dynamics and continuum simulations of the dynamics of relaxation of a fluid system characterized by a non-uniform density profile. Results match quite well as long as the lengthscale of density nonuniformities are greater than the molecular scale (~10 times the molecular size). In presence of molecular scale features some of the continuum fields (e.g., density and momentum) are in good agreement with atomistic counterparts, but are smoother. On the contrary, other fields, such as the temperature field, present very large difference with respect to reference (atomistic) ones. This is due to the limited accuracy of some of the empirical relations used in continuum models, the equation of state of the fluid in the present example.

The local variation of the Gaussian modulus enables different pathways for fluid lipid vesicle fusion.

Viral infections, fertilization, neurotransmission, and many other fundamental biological processes rely on membrane fusion. Straightforward calculations based on the celebrated Canham-Helfrich elastic model predict a large topological energy barrier that prevents the fusion process from being thermally activated. While such high energy is in accordance with the physical barrier function of lipid membranes, it is difficult to reconcile with the biological mechanisms involved in fusion processes. In this work, we use a Ginzburg-Landau type of free energy that recovers the Canham-Helfrich model in the limit of small width-to-vesicle-extension ratio, with the additional ability to handle topological transitions. We show that a local modification of the Gaussian modulus in the merging region both dramatically lowers the elastic energy barrier and substantially changes the minimal energy pathway for fusion, in accordance with experimental evidence. Therefore, we discuss biological examples in which such a modification might play a crucial role.

Mesoscopic elasticity controls dynamin-driven fission of lipid tubules.

Mesoscale physics bridges the gap between the microscopic degrees of freedom of a system and its large-scale continuous behavior and highlights the role of a few key quantities in complex and multiscale phenomena, like dynamin-driven fission of lipid membranes. The dynamin protein wraps the neck formed during clathrin-mediated endocytosis, for instance, and constricts it until severing occurs. Although ubiquitous and fundamental for life, the cooperation between the GTP-consuming conformational changes within the protein and the full-scale response of the underlying lipid substrate is yet to be unraveled. In this work, we build an effective mesoscopic model from constriction to fission of lipid tubules based on continuum membrane elasticity and implicitly accounting for ratchet-like power strokes of dynamins. Localization of the fission event, the overall geometry, and the energy expenditure we predict comply with the major experimental findings. This bolsters the idea that a continuous picture emerges soon enough to relate dynamin polymerization length and membrane rigidity and tension with the optimal pathway to fission. We therefore suggest that dynamins found in in vivo processes may optimize their structure accordingly. Ultimately, we shed light on real-time conductance measurements available in literature and predict the fission time dependency on elastic parameters.

Jingle Cell Rock: Steering Cellular Activity With Low-Intensity Pulsed Ultrasound (LIPUS) to Engineer Functional Tissues in Regenerative Medicine.

Acoustic manipulation or perturbation of biological soft matter has emerged as a promising clinical treatment for a number of applications within regenerative medicine, ranging from bone fracture repair to neuromodulation. The potential of ultrasound (US) endures in imparting mechanical stimuli that are able to trigger a cascade of molecular signals within unscathed cells. Particularly, low-intensity pulsed ultrasound (LIPUS) has been associated with bio-effects such as activation of specific cellular pathways and alteration of cell morphology and gene expression, the extent of which can be modulated by fine tuning of LIPUS parameters including intensity, frequency and exposure time. Although the molecular mechanisms underlying LIPUS are not yet fully elucidated, a number of studies clearly define the modulation of specific ultrasonic parameters as a means to guide the differentiation of a specific set of stem cells towards adult and fully differentiated cell types. Herein, we outline the applications of LIPUS in regenerative medicine and the in vivo and in vitro studies that have confirmed the unbounded clinical potential of this platform. We highlight the latest developments aimed at investigating the physical and biological mechanisms of action of LIPUS, outlining the most recent efforts in using this technology to aid tissue engineering strategies for repairing tissue or modelling specific diseases. Ultimately, we detail tissue-specific applications harnessing LIPUS stimuli, offering insights over the engineering of new constructs and therapeutic modalities. Overall, we aim to lay the foundation for a deeper understanding of the mechanisms governing LIPUS-based therapy, to inform the development of safer and more effective tissue regeneration strategies in the field of regenerative medicine.

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 negative compressibility. 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 hydrophobic 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.

Geometry as a catalyst: how vapor cavities nucleate from defects.

The onset of cavitation is strongly enhanced by the presence of rough surfaces or impurities in the liquid. Despite decades of research, the way the geometry of these defects promote the nucleation of bubbles and its effect on the kinetics of the process remains largely unclear. We present here a comprehensive explanation of the catalytic action that roughness elements exert on the nucleation process for both pure vapor cavities and gas ones. This approach highlights that nucleation may follow nontrivial paths connected with a sharp decrease of the free energy barriers as compared to flat surfaces. Furthermore, we demonstrate the existence of intermediate metastable states that break the nucleation process in multiple steps; these states correspond to what is commonly known as cavitation nuclei. A single dimensionless parameter, the nucleation number, is found to control this rich phenomenology. The devised theory allows one to quantify the effect of the geometry and hydrophobicity of surface asperities on nucleation. Within the same framework, it is possible to treat both vapor cavitation, which is relevant, e.g., for organic liquids, and gas-promoted cavitation, which is commonly encountered in water. The theory is shown to be valid from the nano- to the macroscale.

A nanoscale view of the origin of boiling and its dynamics.

In this work, we present a dynamical theory of boiling based on fluctuating hydrodynamics and the diffuse interface approach. The model is able to describe boiling from the stochastic nucleation up to the macroscopic bubble dynamics. It covers, with a modest computational cost, the mesoscale area from nano to micrometers, where most of the controversial observations related to the phenomenon originate. In particular, the role of wettability in the macroscopic observables of boiling is elucidated. In addition, by comparing the ideal case of boiling on ultra-smooth surfaces with a chemically heterogeneous wall, our results will definitively shed light on the puzzling low onset temperatures measured in experiments. Sporadic nanometric spots of hydrophobic wettability will be shown to be enough to trigger the nucleation at low superheat, significantly reducing the temperature of boiling onset, in line with experimental results. The proposed mesoscale approach constitutes the missing link between macroscopic approaches and molecular dynamics simulations and will open a breakthrough pathway toward accurate understanding and prediction.

Metastable wetting on superhydrophobic surfaces: continuum and atomistic views of the Cassie-Baxter-Wenzel transition.

In this Letter, we develop a continuum theory for the Cassie-Baxter-Wenzel (CB-W) transition. The proposed model accounts for the metastabilities in the wetting of rough hydrophobic surfaces, allows us to reconstruct the transition mechanism, and identifies the free energy barriers separating the CB and W states as a function of the liquid pressure. This information is crucial in the context of superhydrophobic surfaces, where there is interest in extending the duration of the metastable superhydrophobic CB state. The model is validated against free energy atomistic simulations.

Cassie-Baxter and Wenzel states on a nanostructured surface: phase diagram, metastabilities, and transition mechanism by atomistic free energy calculations.

In this work, we study the wetting of a surface decorated with one nanogroove by a bulk Lennard-Jones liquid at various temperatures and densities. We used atomistic simulations aimed at computing the free energy of the stable and metastable states of the system, as well as the intermediate states separating them. We found that the usual description in terms of Cassie-Baxter and Wenzel states is insufficient, as the system presents two states of the Cassie-Baxter type. These states are characterized by different curvatures of the meniscus. The measured free energy barrier separating the Cassie-Baxter from the Wenzel state (and vice versa) largely exceeds the thermal energy, attesting the existence of Cassie-Baxter/Wenzel metastabilities. Finally, we found that the Cassie-Baxter/Wenzel transition follows an asymmetric path, with the formation of a liquid finger on one side of the groove and a vapor bubble on the opposite side.

Activation energy and force fields during topological transitions of fluid lipid vesicles.

Topological transitions of fluid lipid membranes are fundamental processes for cell life. For example, they are required for endo- and exocytosis or to enable neurotransmitters to cross the neural synapses. Here, inspired by the idea that fusion and fission proteins could have evolved in Nature in order to carry out a minimal work expenditure, we evaluate the minimal free energy pathway for the transition between two spherical large unilamellar vesicles and a dumbbell-shaped one. To address the problem, we propose and successfully use a Ginzburg-Landau type of free energy, which allows us to uniquely describe without interruption the whole, full-scale topological change. We also compute the force fields needed to overcome the involved energy barriers. The obtained forces are in excellent agreement, in terms of intensity, scale, and spatial localization with experimental data on typical fission protein systems, whereas they suggest the presence of additional features in fusion proteins.

Turning Molecular Springs into Nano-Shock Absorbers: The Effect of Macroscopic Morphology and Crystal Size on the Dynamic Hysteresis of Water Intrusion-Extrusion into-from Hydrophobic Nanopores.

Controlling the pressure at which liquids intrude (wet) and extrude (dry) a nanopore is of paramount importance for a broad range of applications, such as energy conversion, catalysis, chromatography, separation, ionic channels, and many more. To tune these characteristics, one typically acts on the chemical nature of the system or pore size. In this work, we propose an alternative route for controlling both intrusion and extrusion pressures via proper arrangement of the grains of the nanoporous material. To prove the concept, dynamic intrusion-extrusion cycles for powdered and monolithic ZIF-8 metal-organic framework were conducted by means of water porosimetry and in operando neutron scattering. We report a drastic increase in intrusion-extrusion dynamic hysteresis when going from a fine powder to a dense monolith configuration, transforming an intermediate performance of the ZIF-8 + water system (poor molecular spring) into a desirable shock-absorber with more than 1 order of magnitude enhancement of dissipated energy per cycle. The obtained results are supported by MD simulations and pave the way for an alternative methodology of tuning intrusion-extrusion pressure using a macroscopic arrangement of nanoporous material.