Preservation of human heart valves for replacement in children with heart valve disease: past, present and future.

Valvular heart disease affects 30% of the new-borns with congenital heart disease. Valve replacement of semilunar valves by mechanical, bioprosthetic or donor allograft valves is the main treatment approach. However, none of the replacements provides a viable valve that can grow and/or adapt with the growth of the child leading to re-operation throughout life. In this study, we review the impact of donor valve preservation on moving towards a more viable valve alternative for valve replacements in children or young adults.

From ice-binding proteins to bio-inspired antifreeze materials.

Ice-binding proteins (IBP) facilitate survival under extreme conditions in diverse life forms. IBPs in polar fishes block further growth of internalized environmental ice and inhibit ice recrystallization of accumulated internal crystals. Algae use IBPs to structure ice, while ice adhesion is critical for the Antarctic bacterium Marinomonas primoryensis. Successful translation of this natural cryoprotective ability into man-made materials holds great promise but is still in its infancy. This review covers recent advances in the field of ice-binding proteins and their synthetic analogues, highlighting fundamental insights into IBP functioning as a foundation for the knowledge-based development of cheap, bio-inspired mimics through scalable production routes. Recent advances in the utilisation of IBPs and their analogues to e.g. improve cryopreservation, ice-templating strategies, gas hydrate inhibition and other technologies are presented.

Towards a structural characterization of charge-driven polymer micelles.

Light scattering and small-angle neutron scattering experiments were performed on comicelles of several combinations of oppositely charged (block co)polymers in aqueous solutions. Fundamental differences between the internal structure of this novel type of micelle --termed complex coacervate core micelle (C3Ms), polyion complex (PIC) micelle, block ionomer complex (BIC), or interpolyelectrolyte complex (IPEC)-- and its traditional counterpart, i.e., a micelle formed via self-assembly of polymeric amphiphiles, give rise to differences in scaling behaviour. Indeed, the observed dependencies of micellar size and aggregation number on corona block length, N (corona) , are inconsistent with scaling predictions developed for polymeric micelles in the star-like and crew-cut regime. Generic C3M characteristics, such as the relatively high core solvent fraction, the low core-corona interfacial tension, and the high solubility of the coronal chains, are causing the deviations. A recently proposed scaling theory for the cross-over regime, as well as a primitive first-order self-consistent field (SCF) theory for obligatory co-assembly, follow our data more closely.

Super-resolution microscopy on single particles at fluid interfaces reveals their wetting properties and interfacial deformations.

Solid particles adsorbed at fluid interfaces are crucial for the mechanical stability of Pickering emulsions. The key parameter which determines the kinetic and thermodynamic properties of these colloids is the particle contact angle, θ. Several methods have recently been developed to measure the contact angle of individual particles adsorbed at liquid-liquid interfaces, as morphological and chemical heterogeneities at the particle surface can significantly affect θ. However, none of these techniques enables the simultaneous visualization of the nanoparticles and the reconstruction of the fluid interface to which they are adsorbed, in situ. To tackle this challenge, we utilize a newly developed super-resolution microscopy method, called iPAINT, which exploits non-covalent and continuous labelling of interfaces with photo-activatable fluorescent probes. Herewith, we resolve with nanometer accuracy both the position of individual nanoparticles at a water-octanol interface and the location of the interface itself. First, we determine single particle contact angles for both hydrophobic and hydrophilic spherical colloids. These experiments reveal a non-negligible dependence of θ on particle size, from which we infer an effective line tension, τ. Next, we image elliptical particles at a water-decane interface, showing that the corresponding interfacial deformations can be clearly captured by iPAINT microscopy.

Effects of artepillin C on model membranes displaying liquid immiscibility.

It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (lo) and liquid-disordered (ld) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of lo phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface.

Self-assembly of oppositely charged polyelectrolyte block copolymers containing short thermoresponsive blocks.

The assembly of oppositely charged block copolymers, containing small thermoresponsive moieties, was investigated as a function of salt concentration and temperature. Aqueous solutions of poly-[N-isopropylacrylamide]-b-poly[dimethylaminoethyl methacrylate] (NIPAM44-b-DMAEMA216) and PNIPAM-b-poly[acrylic acid]-b-PNIPAM (NIPAM35-b-AA200-b-NIPAM35) were mixed in equal charge stoichiometry, and analysed by light scattering (LS), NMR spectroscopy and small angle X-ray scattering (SAXS). At room temperature, two different micelle morphologies were found at different salt concentrations. At NaCl concentrations below 0.75 M, complex coacervate core micelles (C3M) with a PNIPAM corona were formed as a result of interpolyelectrolyte complexation. At NaCl concentrations exceeding 0.75 M, the C3M micelles inverted into PNIPAM cored micelles (PCM), containing a water soluble polyelectrolyte corona. This behavior is ascribed to the salt concentration dependence of both the lower critical solution temperature (LCST) of PNIPAM, and the complex coacervation. Above 0.75 M NaCl, the PNIPAM blocks are insoluble in water at room temperature, while complexation between the polyelectrolytes is prevented because of charge screening by the salt. Upon increasing the temperature, both types of micelles display a cloud point temperature (T cp), despite the small thermoresponsive blocks, and aggregate into hydrogels. These hydrogels consist of a complexed polyelectrolyte matrix with microphase separated PNIPAM domains. Controlling the morphology and aggregation of temperature sensitive polyelectrolytes can be an important tool for drug delivery systems, or the application and hardening of underwater glues.

Self-consistent field theory for obligatory coassembly.

We present a first-order model for obligatory coassembly of block copolymers via an associative driving force in a nonselective solvent, making use of the classical self-consistent field (SCF) theory. The key idea is to use a generic associative driving force to bring two polymer blocks together into the core of the micelle and to employ one block of the copolymer(s) to provide a classical stopping mechanism for micelle formation. The driving force is generated by assuming a negative value for the relevant short-range Flory-Huggins interaction parameter. Hence, the model may be adopted to study micellization via H bonding, acceptor-donor interactions, and electrostatic interactions. Here, we limit ourselves to systems that resemble experimental ones where the mechanism of coassembly is electrostatic attraction leading to charge compensation. The resulting micelles are termed complex coacervate core micelles (CCCMs). We show that the predictions are qualitatively consistent with a wide variety of experimentally observed phenomena, even though the model does not yet account for the charges explicitly. For example, it successfully mimics the effect of salt on CCCMs. In the absence of salt CCCMs are far more stable than in excess salt, where the driving force for self-assembly is screened. The main limitations of the SCF model are related to the occurrence of soluble complexes, i.e., soluble, charged particles that coexist with the CCCMs.

Molecular control over colloidal assembly.

Contemporary chemical and material engineering often takes inspiration from nature, targeting for example strong yet light materials and materials composed of highly ordered domains at multiple different lengthscales for fundamental science and applications in e.g. sensing, catalysis, coating technology, and delivery. The preparation of such hierarchically structured functional materials through guided bottom-up assembly of synthetic building blocks requires a high level of control over their synthesis, interactions and assembly pathways. In this perspective we showcase recent work demonstrating how molecular control can be exploited to direct colloidal assembly into responsive materials with mechanical, optical or electrical properties that can be adjusted post-synthesis with external cues.

iPAINT: a general approach tailored to image the topology of interfaces with nanometer resolution.

Understanding interfacial phenomena in soft materials such as wetting, colloidal stability, coalescence, and friction warrants non-invasive imaging with nanometer resolution. Super-resolution microscopy has emerged as an attractive method to visualize nanostructures labeled covalently with fluorescent tags, but this is not amenable to all interfaces. Inspired by PAINT we developed a simple and general strategy to overcome this limitation, which we coin 'iPAINT: interface Point Accumulation for Imaging in Nanoscale Topography'. It enables three-dimensional, sub-diffraction imaging of interfaces irrespective of their nature via reversible adsorption of polymer chains end-functionalized with photo-activatable moieties. We visualized model dispersions, emulsions, and foams with ∼20 nm and ∼3° accuracy demonstrating the general applicability of iPAINT to study solid/liquid, liquid/liquid and liquid/air interfaces. iPAINT thus broadens the scope of super-resolution microscopy paving the way for non-invasive, high-resolution imaging of complex soft materials.

Observation of vibrational energy exchange in a type-III antifreeze protein.

We performed time- and polarization-resolved pump-probe and two-dimensional infrared (2D-IR) experiments to study the dynamics of the amide I vibration of a 7 kDa type-III antifreeze protein. In the pump-probe experiments, we used femtosecond mid-infrared pulses to investigate the vibrational relaxation dynamics of the amide mode. The transient spectra show the presence of two spectral components that decay with different lifetimes, indicative of the presence of two distinct amide subbands. The 2D-IR experiments reveal the coupling between the two bands in the form of cross-peaks. On the basis of previous work by Demirdöven et al. ( J. Am. Chem. Soc. 2004 , 126 , 7981 - 7990 ), we assign the observed bands to the two infrared-active modes α(-) and α(+) found in protein ß-sheets. The amplitudes of the cross-peak were found to increase with delay time, indicating that the cross-peaks originate from population transfer between the coupled amide oscillators. The time constant of the energy transfer was found to be 6-7 ps.

Effects of artepillin C on model membranes displaying liquid immiscibility

It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (lo) and liquid-disordered (ld) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of lo phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface.

Controlling the Cooperativity in the Supramolecular Polymerization of Ionic Discotic Amphiphiles via Electrostatic Screening.

In a combined experimental and theoretical approach, we investigate the supramolecular polymerization of ionic discotic amphiphiles into nanorods of varying mean length, depending on the temperature and ionic strength of the buffered aqueous solution. Invoking a nucleated supramolecular polymerization model that explicitly deals with the effects of screened Coulomb interactions, we correlate the degree of cooperativity of the supramolecular polymerization with the ionic strength of the solution, as probed by means of circular dichroism spectroscopy. Experiment and theory show that electrostatic interactions between the amphiphiles in the rods make the polymerization less cooperative, implying that the larger the concentration of mobile ions in the solution the larger the cooperativity due to their screening effect. We furthermore extract quantitative information about the effective surface charge densities of the supramolecular nanorods in solution, a parameter that has been particularly difficult to determine experimentally in other related self-assembled systems.