Small-Angle Neutron Scattering Reveals the Nanostructure of Liposomes with Embedded OprF Porins of .

The use of liposomes as drug delivery systems emerged in the last decades in view of their capacity and versatility to deliver a variety of therapeutic agents. By means of small-angle neutron scattering (SANS), we performed a detailed characterization of liposomes containing outer membrane protein F (OprF), the main porin of the bacterium outer membrane. These OprF-liposomes are the basis of a novel vaccine against this antibiotic-resistant bacterium, which is one of the main hospital-acquired pathogens and causes each year a significant number of deaths.

Altering Terahertz Sound Propagation in a Liquid upon Nanoparticle Immersion.

One of the grand challenges of new generation Condensed Matter physicists is the development of novel devices enabling the control of sound propagation at terahertz frequency. Indeed, phonon excitations in this frequency window are the leading conveyor of heat transfer in insulators. Their manipulation is thus critical to implementing heat management based on the structural design.

Grasping learning, optimization, and knowledge transfer in the robotics field.

Service robotics is a fast-developing sector, requiring embedded intelligence into robotic platforms to interact with the humans and the surrounding environment. One of the main challenges in the field is robust and versatile manipulation in everyday life activities. An appealing opportunity is to exploit compliant end-effectors to address the manipulation of deformable objects.

The damping of terahertz acoustic modes in aqueous nanoparticle suspensions.

In this work, we investigate the possibility of controlling the acoustic damping in a liquid when nanoparticles are suspended in it. To shed light on this topic, we performed Inelastic X-Ray Scattering (IXS) measurements of the terahertz collective dynamics of aqueous suspensions of nanospheres of various materials, size, and relative concentration, either charged or neutral. A Bayesian analysis of measured spectra indicates that the damping of the two acoustic modes of water increases upon nanoparticle immersion.

Nanostructural Characterization of Cardiolipin-Containing Tethered Lipid Bilayers Adsorbed on Gold and Silicon Substrates for Protein Incorporation.

A key to the development of lipid membrane-based devices is a fundamental understanding of how the molecular structure of the lipid bilayer membrane is influenced by the type of lipids used to build the membrane. This is particularly important when membrane proteins are included in these devices since the precise lipid environment affects the ability to incorporate membrane proteins and their functionality. Here, we used neutron reflectometry to investigate the structure of tethered bilayer lipid membranes and to characterize the incorporation of the NhaA sodium proton exchanger in the bilayer.

A Machine Learning Approach for Mortality Prediction in COVID-19 Pneumonia: Development and Evaluation of the Piacenza Score.

Background: Several models have been developed to predict mortality in patients with COVID-19 pneumonia, but only a few have demonstrated enough discriminatory capacity. Machine learning algorithms represent a novel approach for the data-driven prediction of clinical outcomes with advantages over statistical modeling.

Objective: We aimed to develop a machine learning-based score-the Piacenza score-for 30-day mortality prediction in patients with COVID-19 pneumonia.

Onset of interfacial waves in the terahertz spectrum of a nanoparticle suspension.

We used inelastic x-ray scattering to gain insight into the complex terahertz dynamics of a diluted Au-nanoparticle suspension in glycerol. We observe that, albeit sparse, Au nanoparticles leave clear signatures on the dynamic response of the system, the main one being an additional mode propagating at the nanoparticle-glycerol interface. A Bayesian inferential analysis of the line shape reveals that such a mode, at variance with conventional acoustic modes, keeps a hydrodynamiclike behavior well beyond the continuous limit and down to subnanometer distances.

The Terahertz Dynamics of an Aqueous Nanoparticle Suspension: An Inelastic X-ray Scattering Study.

We used the high-resolution Inelastic X-ray Scattering beamline of the Advanced Photon Source at Argonne National Laboratory to measure the terahertz spectrum of pure water and a dilute aqueous suspension of 15 nm diameter spherical Au nanoparticles (Au-NPs). We observe that, despite their sparse volume concentration of about 0.5%, the immersed NPs strongly influence the collective molecular dynamics of the hosting liquid.

Shedding light on membrane-templated clustering of gold nanoparticles.

The use of inorganic nanoparticles in biomedical and biotechnological applications requires a molecular-level understanding of interactions at nano-bio interfaces, such as cell membranes. Several recent reports have shown that gold nanoparticles (AuNP), in the presence of fluid lipid bilayers, aggregate at the lipid/aqueous interface, but the precise origin of this phenomenon is still not fully understood. Here, by challenging synthetic lipid membranes with one of the most typical classes of nanomaterials, citrate-coated AuNP, we addressed the cooperative nature of their interaction at the interface, which leads to AuNP clustering.

Neutron spin echo monitoring of segmental-like diffusion of water confined in the cores of carbon nanotubes.

Following the stream of increasing scientific interest in condensed-matter systems under ultra-hydrophobic confinement, the present work reports the first incoherent neutron spin echo assessment of the dynamics of water axially confined inside single-wall carbon nanotubes of diameter d∼ 1.4 nm. At the time scale of nanoseconds, two water populations are retrieved, whose relative proportion matches the one expected for a concentric shell + chain arrangement with cylindrical symmetry.

Interpreting the Terahertz Spectrum of Complex Materials: The Unique Contribution of the Bayesian Analysis.

In the last few decades, experimental studies of the terahertz spectrum of density fluctuations have considerably improved our knowledge of the mesoscopic dynamics of disordered materials, which also have imposed new demands on the data modelling and interpretation. Indeed, lineshape analyses are no longer limited to the phenomenological observation of inelastic features, as in the pioneering stage of Neutron or X-ray spectroscopy, rather aiming at the extraction from their shape of physically relevant quantities, as sound velocity and damping, relaxation times, or other transport coefficients. In this effort, researchers need to face both inherent and practical obstacles, respectively stemming from the highly damped nature of terahertz modes and the limited energy resolution, accessible kinematic region and statistical accuracy of the typical experimental outcome.

Model-free description of polymer-coated gold nanoparticle dynamics in aqueous solutions obtained by Bayesian analysis of neutron spin echo data.

We present a neutron spin echo study of the nanosecond dynamics of polyethylene glycol (PEG) functionalized nanosized gold particles dissolved in D_{2}O at two temperatures and two different PEG molecular weights (400D and 2000D). The analysis of the neutron spin echo data was performed by applying a Bayesian approach to the description of time correlation function decays in terms of exponential terms, recently proved to be theoretically rigorous. This approach, which addresses in a direct way the fundamental issue of model choice in any dynamical analysis, provides here a guide to the most statistically supported way to follow the decay of the intermediate scattering functions I(Q,t) by basing on statistical grounds the choice of the number of terms required for the description of the nanosecond dynamics of the studied systems.

The Role of Temperature and Lipid Charge on Intake/Uptake of Cationic Gold Nanoparticles into Lipid Bilayers.

Understanding the molecular mechanisms governing nanoparticle-membrane interactions is of prime importance for drug delivery and biomedical applications. Neutron reflectometry (NR) experiments are combined with atomistic and coarse-grained molecular dynamics (MD) simulations to study the interaction between cationic gold nanoparticles (AuNPs) and model lipid membranes composed of a mixture of zwitterionic di-stearoyl-phosphatidylcholine (DSPC) and anionic di-stearoyl-phosphatidylglycerol (DSPG). MD simulations show that the interaction between AuNPs and a pure DSPC lipid bilayer is modulated by a free energy barrier.

Amyloid β-Peptide Interaction with Membranes: Can Chaperones Change the Fate?

The understanding of amyloid β-peptide (Aβ) interactions with cellular membranes is a crucial molecular challenge against Alzheimer's disease. Indeed, Aβ prefibrillar oligomeric intermediates are believed to be the most toxic species, able to induce cellular damages directly by membrane damage. We present a neutron-scattering study on the interaction of large unilamellar vesicles (LUV), as cell membrane models, with both freshly dissolved Aβ and early toxic prefibrillar oligomers, intermediate states in the amyloid pathway.

Damping Off Terahertz Sound Modes of a Liquid upon Immersion of Nanoparticles.

The control of phonon propagation in nanoparticle arrays is one of the frontiers of nanotechnology, potentially enabling the discovery of materials with unknown functionalities for potential innovative applications. The exploration of the terahertz window appears quite promising as phonons in this range are the leading carriers of heat transport in insulators and their control is the key to implement devices for heat flow management. Unfortunately, this scientific field is still in its infancy, and even a basic topic such as the influence of floating nanoparticles on the terahertz phonon propagation of a colloidal suspension still eludes a firm answer.

Temperature-dependent structure and dynamics of highly-branched poly(N-isopropylacrylamide) in aqueous solution.

Small-angle neutron scattering (SANS) and neutron spin-echo (NSE) have been used to investigate the temperature-dependent solution behaviour of highly-branched poly(N-isopropylacrylamide) (HB-PNIPAM). SANS experiments have shown that water is a good solvent for both HB-PNIPAM and a linear PNIPAM control at low temperatures where the small angle scattering is described by a single correlation length model. Increasing the temperature leads to a gradual collapse of HB-PNIPAM until above the lower critical solution temperature (LCST), at which point aggregation occurs, forming disperse spherical particles of up to 60 nm in diameter, independent of the degree of branching.

Functional Characterization of Cell-Free Expressed OprF Porin from Pseudomonas aeruginosa Stably Incorporated in Tethered Lipid Bilayers.

OprF has a central role in Pseudomonas aeruginosa virulence and thus provides a putative target for either vaccines or antibiotic cofactors that could overcome the bacterium's natural resistance to antibiotics. Here we describe a procedure to optimize the production of highly pure and functional OprF porins that are then incorporated into a tethered lipid bilayer. This is a stable biomimetic system that provides the capability to investigate structural aspects and function of OprF using and neutron reflectometry and electrical impedance spectroscopy.

The effect of the protein corona on the interaction between nanoparticles and lipid bilayers.

Hypothesis: It is known that nanoparticles (NPs) in a biological fluid are immediately coated by a protein corona (PC), composed of a hard (strongly bounded) and a soft (loosely associated) layers, which represents the real nano-interface interacting with the cellular membrane in vivo. In this regard, supported lipid bilayers (SLB) have extensively been used as relevant model systems for elucidating the interaction between biomembranes and NPs. Herein we show how the presence of a PC on the NP surface changes the interaction between NPs and lipid bilayers with particular care on the effects induced by the NPs on the bilayer structure.

Thermal activation of 'allosteric-like' large-scale motions in a eukaryotic Lactate Dehydrogenase.

Conformational changes occurring during the enzymatic turnover are essential for the regulation of protein functionality. Individuating the protein regions involved in these changes and the associated mechanical modes is still a challenge at both experimental and theoretical levels. We present here a detailed investigation of the thermal activation of the functional modes and conformational changes in a eukaryotic Lactate Dehydrogenase enzyme (LDH).

Modulation of hemoglobin dynamics by an allosteric effector.

Hemoglobin (Hb) is an extensively studied paradigm of proteins that alter their function in response to allosteric effectors. Models of its action have been used as prototypes for structure-function relationships in many proteins, and models for the molecular basis of its function have been deeply studied and extensively argued. Recent reports suggest that dynamics may play an important role in its function.

Nanostructural determination of a lipid bilayer tethered to a gold substrate.

Tethered lipid bilayer membranes (tBLM) are planar membranes composed of free lipids and molecules tethered to a solid planar substrate providing a useful model of biological membranes for a wide range of biophysical studies and biotechnological applications. The properties of the tBLM depend on the free lipids and on the chemistry of the tethering molecules. We present a nanoscale characterization of a tBLM composed of deuterated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (d-DMPC) free lipids, benzyl disulfide undecaethylene glycol phytanol (DLP) tethering molecules, and benzyl disulfiide tetraethylene glycol polar spacer molecules (PSM) used to control the areal density of tethering molecules through coadsorption.

The Search for Nanobubbles by Using Specular and Off-Specular Neutron Reflectometry.

We apply specular and off-specular neutron reflection at the hydrophobic silicon/water interface to check for evidence of nanoscopic air bubbles whose presence is claimed after an ad hoc procedure of solvent exchange. Nanobubbles and/or a depletion layer at the hydrophobic/water interface have long been discussed and generated a plethora of controversial scientific results. By combining neutron reflectometry (NR), off-specular reflectometry (OSS), and grazing incidence small angle neutron scattering (GISANS), we studied the interface between hydrophobized silicon and heavy water before and after saturation with nitrogen gas.

Submicrometer 3D Structural Evidence of Fuel Cell Membrane Heterogeneous Degradation.

Polymer membranes used in the proton exchange membrane fuel cell (PEMFC) technology are subject to severe chemical and physical degradations during operation. A microscopic diagnosis of the effects of aging on the microstructure of benchmark perfluorinated sulfonic acid (PFSA) membranes is crucial to developing long-lasting devices. We report here the first μSAXS study of membranes aged for 2500 h in a stack.

Effect of functionalized gold nanoparticles on floating lipid bilayers.

The development of novel nano-engineered materials poses important questions regarding the impact of these new materials on living systems. Possible adverse effects must be assessed in order to prevent risks for health and the environment. On the other hand, a thorough understanding of their interaction with biological systems might also result in the creation of novel biomedical applications.

Solid surface structure affects liquid order at the polystyrene-self-assembled-monolayer interface.

We present a combined x-ray and neutron reflectivity study characterizing the interface between polystyrene (PS) and silanized surfaces. Motivated by the large difference in slip velocity of PS on top of dodecyl-trichlorosilane (DTS) and octadecyl-trichlorosilane (OTS) found in previous studies, these two systems were chosen for the present investigation. The results reveal the molecular conformation of PS on silanized silicon.