Unraveling dispersion and buoyancy dynamics around radial A + B → C reaction fronts: microgravity experiments and numerical simulations.

Radial Reaction-Diffusion-Advection (RDA) fronts for A + B → C reactions find wide applications in many natural and technological processes. In liquid solutions, their dynamics can be perturbed by buoyancy-driven convection due to concentration gradients across the front. In this context, we conducted microgravity experiments aboard a sounding rocket, in order to disentangle dispersion and buoyancy effects in such fronts. We studied experimentally the dynamics due to the radial injection of A in B at a constant flow rate, in absence of gravity. We compared the obtained results with numerical simulations using either radial one- (1D) or two-dimensional (2D) models. We showed that gravitational acceleration significantly distorts the RDA dynamics on ground, even if the vertical dimension of the reactor and density gradients are small. We further quantified the importance of such buoyant phenomena. Finally, we showed that 1D numerical models with radial symmetry fail to predict the dynamics of RDA fronts in thicker geometries, while 2D radial models are necessary to accurately describe RDA dynamics where Taylor-Aris dispersion is significant.

Population Mass Balance Model for Precipitation with Turbidity Measurements.

The discretized population balance theory has been proven to be a useful method to simulate systems in which solid particles are present. In this work, we introduce a new approach to model precipitation reactions based on the temporal evolution of product concentration, from which particle size distribution, its dynamics, and the specific interfacial energies can be obtained. For a reference study, the previously investigated calcium oxalate precipitation was selected, where the reaction was followed via turbidity measurement. From the obtained particle size distribution, we can show that at low supersaturation, growth is the dominant process, while at higher supersaturation, nucleation is the dominant process. Moreover, the temporal change of the distribution curve has allowed us to split the precipitation into a nucleation, a growth-driven intermediate, and a saturation regime. Furthermore, the comparison between the experimental and calculated results has proved that the method is suitable for predicting particle size distributions and specific interfacial energies.

Oscillatory dynamics in a reaction network based on imine hydrolysis.

We have built an autocatalytic reaction network, based on the hydrolysis of certain imines, which exhibits bistability in an open system. The positive feedback originates from the interplay of fast acid-base equilibria, leading to hydroxide ion production, and pH-dependent hydrolysis rates. The addition of a first-order removal of the autocatalyst can result in sustained pH oscillations close to physiological conditions. The unit-amplitude pH oscillations are accompanied by the stoichiometric conversion of imine into amine back and forth. A systematic parameter search is carried out to characterize the rich observable dynamics and identify the evolving bifurcations.

Self-propulsion of a calcium alginate surfer.

A droplet of sodium alginate dripped into calcium chloride solution results in plate or boat shaped hydrogels. Both exhibit several minute-long self-propelled motion on the liquid surface without any extra fuel added, offering a new method to making active materials. By changing the initial concentrations, we are able to tune the transient dynamic activities from translational to rotational or stop-and-run motion. Dynamics are governed by osmotic pressure induced Marangoni effect, depending on the density difference and initial concentrations.

Dynamics of hydroxide-ion-driven reversible autocatalytic networks.

In living systems adaptive regulation requires the presence of nonlinear responses in the underlying chemical networks. Positive feedbacks, for example, can lead to autocatalytic bursts that provide switches between two stable states or to oscillatory dynamics. The stereostructure stabilized by hydrogen bonds provides an enzyme its selectivity, rendering pH regulation essential for its functioning. For effective control, triggers by small concentration changes play roles where the strength of feedback is important. Here we show that the interaction of acid-base equilibria with simple reactions with pH-dependent rate can lead to the emergence of a positive feedback in hydroxide ion concentration during the hydrolysis of some Schiff bases in the physiological pH range. The underlying reaction network can also support bistability in an open system.

Self-assembly to synchrony of active gels.

Self-assembly functionalizes active constituents to perform rhythmic activities. Here, our results show that the capillary-Marangoni interaction of irregularly moving gel beads develops complex patterns at the air-liquid interface. The collective behavior of the self-assembled structures exhibits breathing dynamics, polygonal oscillating rings, and cluster synchrony of chains. Interestingly, the trapping of soft particles generates relay synchronization of a rotor. Swarming of clusters is found to form rhythmic shrinking and expanding multiple-ring patterns. The development of self-organized spatiotemporal patterns of our active gel system provides a new way of creating collective oscillations.

Computational and structural insights into the pre- and post-hydrolysis states of bovine multidrug resistance-associated protein 1.

ATP-binding cassette C-family drug membrane transporters play an important role in local pharmacokinetics, that is, drug concentration in cellular compartments. From the structural point of view, only the bovine ortholog of the multidrug resistance-associated protein 1 (bMRP1) has been resolved. We here used µs-scaled molecular dynamics simulations to investigate the structure and dynamics of the bovine multidrug resistance-associated protein 1 in pre- and post-hydrolysis functional states. The present work aims to examine the slight but likely relevant structural differences between pre- and post-hydrolysis states of outward-facing conformations as well as the interactions between the multidrug resistance-associated protein 1 and the surrounding lipid bilayer. Global conformational dynamics show unfavourable extracellular opening associated with nucleotide-binding domain dimerization indicating that the post-hydrolysis state adopts a close-cleft conformation rather than an outward-open conformation. Our present simulations also highlight persistent interactions with annular cholesterol molecules and the expected active role of lipid bilayer in the allosteric communication between distant domains of the transporter.

From Balloon to Crystalline Structure in the Calcium Phosphate Flow-Driven Chemical Garden.

We have studied the calcium phosphate precipitation reaction by producing chemical gardens in a controlled manner using a three-dimensional flow-driven technique. The injection of the phosphate containing solution into the calcium ion reservoir has resulted in structures varying from membranes to crystals. Dynamical phase diagrams are constructed by varying chemical composition and flow rates from which three different growth mechanisms have been revealed. The microstructural analysis by scanning electron microscopy and powder X-ray diffraction confirmed the morphological transition from membrane tubes to crystalline branches upon decreasing pH.

On the interplay between lipids and asymmetric dynamics of an NBS degenerate ABC transporter.

Multidrug resistance-associated proteins are ABC C-family exporters. They are crucial in pharmacology as they transport various substrates across membranes. However, the role of the degenerate nucleotide-binding site (NBS) remains unclear likewise the interplay with the surrounding lipid environment. Here, we propose a dynamic and structural overview of MRP1 from ca. 110 µs molecular dynamics simulations. ATP binding to NBS1 is likely maintained along several transport cycles. Asymmetric NBD behaviour is ensured by lower signal transduction from NBD1 to the rest of the protein owing to the absence of ball-and-socket conformation between NBD1 and coupling helices. Even though surrounding lipids play an active role in the allosteric communication between the substrate-binding pocket and NBDs, our results suggest that lipid composition has a limited impact, mostly by affecting transport kinetics. We believe that our work can be extended to other degenerate NBS ABC proteins and provide hints for deciphering mechanistic differences among ABC transporters.

Substrate binding and lipid-mediated allostery in the human organic anion transporter 1 at the atomic-scale.

The Organic Anion Transporter 1 is a membrane transporter known for its central role in drug elimination by the kidney. hOAT1 is an antiporter translocating substrate in exchange for a-ketoglutarate. The understanding of hOAT1 structure and function remains limited due to the absence of resolved structure of hOAT1. Benefiting from conserved structural and functional patterns shared with other Major Facilitator Superfamily transporters, the present study intended to investigate fragments of hOAT1 transport function and modulation of its activity in order to make a step forward the understanding of its transport cycle. µs-long molecular dynamics simulation of hOAT1 were carried out suggesting two plausible binding sites for a typical substrate, adefovir, in line with experimental observations. The well-known B-like motif binding site was observed in line with previous studies. However, we here propose a new inner binding cavity which is expected to be involved in substrate translocation event. Binding modes of hOAT1 co-substrate α-ketoglutarate were also investigated suggesting that it may bind to highly conserved intracellular motifs. We here hypothesise that α-ketoglutarate may disrupt the pseudo-symmetrical intracellular charge-relay system which in turn may participate to the destabilisation of OF conformation. Investigations regarding allosteric communications along hOAT1 also suggest that substrate binding event might modulate the dynamics of intracellular charge relay system, assisted by surrounding lipids as active partners. We here proposed a structural rationalisation of transport impairments observed for two single nucleotide polymorphisms, p.Arg50His and p.Arg454Gln suggesting that the present model may be used to transport dysfunctions arising from hOAT1 mutations.

Flow-driven synthesis of calcium phosphate-calcium alginate hybrid chemical gardens.

Systems far-from-equilibrium self-assemble into spatiotemporal structures. Here, we report on the formation of calcium alginate gardens along with their inorganic hybrids when a sodium alginate solution containing sodium phosphate in various compositions is injected into a calcium chloride reservoir. The viscoelastic properties of the membranes developed are controlled by the injection rate, while their thickness by the amount of sodium phosphate besides diffusion. Inorganic hybrid membranes with constant thickness are synthesized in the presence of a sufficient amount of sodium phosphate. The electrochemical characterization of the membranes suggests that the driving force is the pH-gradient developing along the two sides; hence, the cell potential can be controlled by the addition of alkaline sodium phosphate into the sodium alginate solution.

Sol-gel transition programmed self-propulsion of chitosan hydrogel.

Active soft materials exhibit various dynamics ranging from boat pulsation to thin membrane deformation. In the present work, in situ prepared ethanol-containing chitosan gels propel in continuous and intermittent motion. The active life of the organic material loaded to the constant fuel level follows a linear scaling, and its maximal velocity and projection area decrease steeply with chitosan concentration. A thin propelling platelet forms at low polymer content, leading to the suppression of intermittent motion. Moreover, the fast accelerating thin gels can split into a crescent and circular-like shape or fission into multiple asymmetric fragments.

Collective motion of self-propelled chemical garden tubes.

In H2O2 solutions, manganese-containing chemical garden tubes can self-propel due to the catalytic production and ejection of oxygen bubbles. Here, we investigate the collective behavior of these self-assembled precipitate tubes. In thin solution layers, the tubes show definite autonomous dynamics with only weak interactions that result from fluid motion around the moving units and directional changes during collisions. In thick solution layers with convex menisci forcing spatial confinement, the tubes undergo cycles of self-assembly and dispersion. This collective motion results from the rhythmic creation of a large master bubble around which the tubes align tangentially.

Phospholipid-porphyrin conjugates: deciphering the driving forces behind their supramolecular assemblies.

Phospholipid-porphyrin conjugates (PL-Por) are nowadays considered as a unique class of building blocks that can self-assemble into supramolecular structures that possess multifunctional properties and enhanced optoelectronics characteristics compared to their disassembled counterparts. However, despite their versatile properties, little is known about the impact of the packing parameter of PL-Por conjugates on their assembling mechanism and their molecular organization inside these assemblies. To gain a better understanding on their assembling properties, we synthesized two new series of PL-Por conjugates with different alkyl sn2-chain lengths linked via an amide bond to either pheophorbide-a (PhxLPC) or pyropheophorbide-a (PyrxLPC). By combining a variety of experimental techniques with molecular dynamics (MD) simulations, we investigated both the assembling and optical properties of the PL-Por either self-assembled or when incorporated into lipid bilayers. We demonstrated that independently of the linker length, PhxLPC assembled into closed ovoid structures, whereas PyrxLPC formed rigid open sheets. Interestingly, PyrxLPC assemblies displayed a significant red shift and narrowing of the Q-band indicating the formation of ordered J-aggregates. The MD simulations highlighted the central role of the interaction between porphyrin cores rather than the length difference between the two phospholipid chains in controlling the structure of the lipid bilayer membranes and thus their optical properties. Indeed, while PhxLPC have the tendency to form inter-leaflet π-stacked dimers, PyrxLPC conjugates formed dimers within the same leaflet. Altogether, this work could be used as guidelines for the design of new PL-Por conjugates that self-assemble into bilayer-like supramolecular structures with tunable morphology and optical properties.

Application of a chemical clock in material design: chemically programmed synthesis of zeolitic imidazole framework-8.

Here we show a time-programmed and autonomous synthesis of zeolitic imidazole framework-8 (ZIF-8) using a methylene glycol-sulfite clock reaction. The induction period of the driving clock reaction, thus, the appearance of the ZIF-8 can be adjusted by the initial concentration of one reagent of the chemical clock. The autonomously synthesized ZIF-8 showed excellent morphology and crystallinity.

Pattern selection of directionally oriented chitosan tubes.

The growth of viscoelastic curved materials, inspired by biological systems, may give rise to various complex structures. One of the simplest ways to control the pattern formation is to vary the orientation of the reaction vessel while keeping all other experimental conditions constant. Here, we report the self-organization of soft chitosan tubes by injecting acidic chitosan sol into a pool of sodium hydroxide solution, where the adhesive force between the gel and container keeps the tubules on the bottom of the reactor. The horizontal growth of the tubular structure undergoes spontaneous symmetry breaking, where instabilities develop on the surface of the chitosan tubules. Transformation of folds into wrinkles and finally to a smooth tube takes place by varying the orientation of the container. In addition to characterizing the evolving structures, we have also shown that the linear growth rate of the tube scales with the tilt angle of the container from the horizontal.

Insights into the structure and function of the human organic anion transporter 1 in lipid bilayer membranes.

The human SLC22A6/OAT1 plays an important role in the elimination of a broad range of endogenous substances and xenobiotics thus attracting attention from the pharmacological community. Furthermore, OAT1 is also involved in key physiological events such as the remote inter-organ communication. Despite its significance, the knowledge about hOAT1 structure and the transport mechanism at the atomic level remains fragmented owing to the lack of resolved structures. By means of protein-threading modeling refined by µs-scaled Molecular Dynamics simulations, the present study provides the first robust model of hOAT1 in outward-facing conformation. Taking advantage of the AlphaFold 2 predicted structure of hOAT1 in inward-facing conformation, we here provide the essential structural and functional features comparing both states. The intracellular motifs conserved among Major Facilitator Superfamily members create a so-called "charge-relay system" that works as molecular switches modulating the conformation. The principal element of the event points at interactions of charged residues that appear crucial for the transporter dynamics and function. Moreover, hOAT1 model was embedded in different lipid bilayer membranes highlighting the crucial structural dependence on lipid-protein interactions. MD simulations supported the pivotal role of phosphatidylethanolamine components to the protein conformation stability. The present model is made available to decipher the impact of any observed polymorphism and mutation on drug transport as well as to understand substrate binding modes.

Formation and growth of lithium phosphate chemical gardens.

We show that a chemical garden can be developed from an alkaline metal precipitate using a flow-driven setup. By injecting sodium phosphate solution into lithium chloride solution from below, a liquid jet appears, on which a precipitate grows forming a structure resembling a hydrothermal vent. The precipitate column continuously builds upward until a maximum height is reached. The vertical growth then significantly slows down while the tube diameter still increases. The analysis of the growth profiles has revealed a linear dependence of volume growth rate on the injection rate, hence yielding a universal growth profile. The expansion in diameter, localized at the tip of the structure, scales with a power law suggesting that the phenomenon is controlled by both diffusion and convection.

Synthesis of zeolitic imidazolate framework-8 and gold nanoparticles in a sustained out-of-equilibrium state.

The design and synthesis of crystalline materials are challenging due to the proper control over the size and polydispersity of the samples, which determine their physical and chemical properties and thus applicability. Metal - organic frameworks (MOFs) are promising materials in many applications due to their unique structure. MOFs have been predominantly synthesized by bulk methods, where the concentration of the reagents gradually decreased, which affected the further nucleation and crystal growth. Here we show an out-of-equilibrium method for the generation of zeolitic imidazolate framework-8 (ZIF-8) crystals, where the non-equilibrium crystal growth is maintained by a continuous two-side feed of the reagents in a hydrogel matrix. The size and the polydispersity of the crystals are controlled by the fixed and antagonistic constant mass fluxes of the reagents and by the reaction time. We also present that our approach can be extended to synthesize gold nanoparticles in a redox process.

Origins of oscillatory dynamics in the model of reactive oxygen species in the rhizosphere.

Oscillatory processes are essential for normal functioning and survival of biological systems, and reactive oxygen species have a prominent role in many of them. A mechanism representing the dynamics of these species in the rhizosphere is analyzed using stoichiometric network analysis with the aim to determine its capabilities to simulate various dynamical states, including oscillations. A detailed analysis has shown that unstable steady states result from four destabilizing feedback cycles, among which the cycle involving hydroquinone, an electron acceptor, and its semi-reduced form is the dominant one responsible for the existence of saddle-node and Andronov-Hopf bifurcations. This requires a higher steady-state concentration for the reduced electron acceptor compared to that of the remaining species, where the level of oxygen steady-state concentration determines whether the Andronov-Hopf or saddle-node bifurcation will occur.