Energetic Coupling Research Articles

Modulating long-range energetics via helix stabilization: A case study using T4 lysozyme.

Cooperative protein folding requires distant regions of a protein to interact and provide mutual stabilization. The mechanism of this long-distance coupling remains poorly understood. Here, we use T4 lysozyme (T4L*) as a model to investigate long-range communications across two subdomains of a globular protein. T4L* is composed of two structurally distinct subdomains, although it behaves in a two-state manner at equilibrium. The subdomains of T4L* are connected via two topological connections: the N-terminal helix that is structurally part of the C-terminal subdomain (the A-helix) and a long helix that spans both subdomains (the C-helix). To understand the role that the C-helix plays in cooperative folding, we analyzed a circularly permuted version of T4L* (CP13*), whose subdomains are connected only by the C-helix. We demonstrate that when isolated as individual fragments, both subdomains of CP13* can fold autonomously into marginally stable conformations. The energetics of the N-terminal subdomain depend on the formation of a salt bridge known to be important for stability in the full-length protein. We show that the energetic contribution of the salt bridge to the stability of the N-terminal fragment increases when the C-helix is stabilized, such as occurs upon folding of the C-terminal subdomain. These results suggest a model where long-range energetic coupling is mediated by helix stabilization and not specific tertiary interactions.

Novel type of ferroelectricity in brownmillerite structures: A first-principles study

First-principles calculations are conducted on two magnetic brownmillerites, namely, ${\mathrm{Ca}}_{2}{\mathrm{Co}}_{2}{\mathrm{O}}_{5}$ and ${\mathrm{Sr}}_{2}{\mathrm{Co}}_{2}{\mathrm{O}}_{5}$. Both systems possess a previously overlooked polar $Pmc{2}_{1}$ phase that is low in energy. This ferroelectric state is even predicted to be the ground state of ${\mathrm{Sr}}_{2}{\mathrm{Co}}_{2}{\mathrm{O}}_{5}$, which therefore renders such material multiferroic. Strikingly, the ferroelectricity associated with this $Pmc{2}_{1}$ phase involves an original energetic coupling that is linear in the polar mode, quadratic in another distortion, and linear in a third mode. Such ferroelectricity is therefore of a novel type, since it differs from previously reported proper, improper, hybrid improper, and triggered kinds of ferroelectricity.

A CdSe/ZnS quantum dot-based platform for the delivery of aluminum phthalocyanines to bacterial cells

Enhancement of optical properties of photosensitizers by additional light-harvesting antennas is promising for the improvement of the photodynamic therapy. However, large number of parameters determine interactions of nanoparticles and photosensitizers in complex and, thus the photodynamic efficacy of the hybrid structure. In order to achieve high efficiency of energetic coupling and photodynamic activity of such complexes it is important to know the location of the photosensitizer molecule on the nanoparticle, because it affects the spectral properties of the photosensitizer and the stability of the hybrid complex in vitro/in vivo. In this work complexes of polycationic aluminum phthalocyanines and CdSe/ZnS quantum dots were obtained. We used quantum dots which outer shell consists of polymer with carboxyl groups and provides water solubility and the negative charge of the nanoparticle. We found that phthalocyanine molecules could penetrate deeply into the polymer shell of quantum dot, leading thereby to significant changes in the spectral and photodynamic properties of phthalocyanines. We also showed that noncovalent interactions between phthalocyanine and quantum dot provide possibility for a release of the phthalocyanine from the hybrid complex and its binding to both Gram-positive and Gram-negative bacterial cells. Also, detailed characterization of the nanoparticle core and shell sizes was carried out.

Short‐Term and Interannual Variations of Migrating Diurnal and Semidiurnal Tides in the Mesosphere and Lower Thermosphere

AbstractAmong the broad spectrum of vertically propagating tides, migrating diurnal (DW1) and semidiurnal (SW2) are prominent modes of energetic and dynamical coupling between the mesosphere and lower thermosphere and the upper thermosphere and ionosphere. DW1 and SW2 tides are modulated on time scales ranging from days to years. NASA Thermosphere‐Ionosphere‐Mesosphere Energetic and Dynamics (TIMED) is the first observational platform to perform global synoptic observations of these fundamental tides (for nearly two decades) overcoming previous observational limitations. Here we utilize the extensive archive of TIMED Doppler Interferometer wind measurements and exploit the capabilities of tidal theory to estimate short‐term (<1 month), seasonal (intra‐annual), long‐term (>1 year), and climatological variability in DW1 (1,1), SW2 (2,2), and SW2 (2,3) modes and then compare with tidal estimates derived from the Navy Global Environmental Model‐High Altitude version data assimilation system. Overall, the tidal estimates from TIMED Doppler Interferometer and Navy Global Environmental Model‐High Altitude version are similar and exhibit significant short‐term and intra‐annual variability. The short‐term variability can induce ∼64% change in the DW1 amplitude. Statistically, the short‐term variability in DW1 (1,1), SW2 (2,2), and SW2 (2,3) modes is of the order of ∼9, 33, and 20 m/s, respectively. The biennial oscillations in DW1 and SW2 modes suggest a systematic correlation with the equatorial quasi‐biennial oscillation in the stratosphere and are more apparent in DW1 amplitudes. Although there is significant interannual variability in addition to the apparent biennial signal, there is no clear evidence of any solar cycle dependence or long‐term trend in either DW1 or SW2 modes.

Outsized stochasticity of iodine oxidation with hydrogen peroxide and its implications on the reaction mechanism

We examined the most interesting subsystem of the Bray-Liebhafsky (BL) oscillator i.e. oxidation of iodine to iodate in acidic media with hydrogen peroxide. The reaction induction periods and formed iodate are characterized by potentiometric method and stopped-flow technique. Introduction of a very slow mixing, at 27 °C, increased standard deviation of results to 124 from 2.5 in experiments without mixing. It is confirmed at two lower temperatures. In such (initially) simple chemical system the stochasticity is related with random fluctuations forming critical oxygen cavities. Possible energetic coupling of the nucleation processes with chemical reactions is discussed in connection with previous results.

Ensemble allosteric model: energetic frustration within the intrinsically disordered glucocorticoid receptor.

Allostery is an important regulatory phenomenon enabling precise control of biological function. Initial understanding of allostery was gained from seminal work on conformational changes exhibited by structured proteins. Within the last decade, protein allostery has also been demonstrated to occur within intrinsically disordered proteins. This emerging concept of disorder-mediated allostery can be usefully understood in the context of a thermodynamic ensemble. The advantage of this ensemble allosteric model is that it unifies the explanations of allostery occurring within both structured and disordered proteins. One central finding from this model is that energetic coupling, the transmission of a signal between separate regions (or domains) of a protein, is maximized when one or more domains are disordered. This is due to a disorder-order transition that contributes additional coupling energy to the allosteric system through formation of a molecular interaction surface or interface. A second key finding is that multiple interfaces may constructively or destructively interfere with each other, resulting in a new form of allosteric regulation called 'energetic frustration'. Articulating protein allostery in terms of the thermodynamic ensemble permits formulation of experimentally testable hypotheses which can increase fundamental understanding and direct drug-design efforts. These ideas are illustrated here with the specific case of human glucocorticoid receptor, a medically important multi-domain allosteric protein that contains both structured and disordered regions and exemplifies 'energetic frustration'.This article is part of a discussion meeting issue 'Allostery and molecular machines'.

Novel heparin mimetics reveal cooperativity between exosite 2 and sodium-binding site of thrombin

IntroductionThrombin is a primary target of most anticoagulants. Yet, thrombin's dual and opposing role in pro- as well as anti- coagulant processes imposes considerable challenges in discovering finely tuned regulators that maintain homeostasis, rather than disproportionately changing the equilibrium to one side. In this connection, we have been studying exosite 2-mediated allosteric modulation of thrombin activity using synthetic agents called low molecular weight lignins (LMWLs). Although the aromatic scaffold of LMWLs is completely different from the polysaccharidic scaffold of heparin, the presence of multiple negatively charged groups on both ligands induces binding to exosite 2 of thrombin. This work characterizes the nature of interactions between LMWLs and thrombin to understand the energetic cooperativity between exosite 2 and active site of thrombin. Materials and methodsThe thermodynamics of thrombin–LMWL complexes was studied using spectrofluorimetric titrations as a function of ionic strength and temperature of the buffer. The contributions of enthalpy and entropy to binding were evaluated using classic thermodynamic equations. Label-free surface plasmon resonance was used to assess the role of sodium ion in LMWL binding to thrombin at a fixed ionic strength. Results and conclusionsExosite 2-induced conformational change in thrombin's active site is strongly dependent on the structure of the ligand, which has consequences with respect to regulation of thrombin. The ionic and non-ionic contributions to binding affinity and the thermodynamic signature were highly ligand specific. Interestingly, LMWLs display preference for the sodium-bound form of thrombin, which supports the existence of an energetic coupling between exosite 2 and sodium-binding site of thrombin.

An allosteric link connecting the lipid-protein interface to the gating of the nicotinic acetylcholine receptor

The mechanisms underlying lipid-sensing by membrane proteins is of considerable biological importance. A unifying mechanistic question is how a change in structure at the lipid-protein interface is translated through the transmembrane domain to influence structures critical to protein function. Gating of the nicotinic acetylcholine receptor (nAChR) is sensitive to its lipid environment. To understand how changes at the lipid-protein interface influence gating, we examined how a mutation at position 418 on the lipid-facing surface of the outer most M4 transmembrane α-helix alters the energetic couplings between M4 and the remainder of the transmembrane domain. Human muscle nAChR is sensitive to mutations at position 418, with the Cys-to-Trp mutation resulting in a 16-fold potentiation in function that leads to a congenital myasthenic syndrome. Energetic coupling between M4 and the Cys-loop, a key structure implicated in gating, do not change with C418W. Instead, Trp418 and an adjacent residue couple energetically with residues on the M1 transmembrane α-helix, leading to a reorientation of M1 that stabilizes the open state. We thus identify an allosteric link connecting the lipid-protein interface of the nAChR to altered channel function.

A triad of residues is functionally transferrable between 5-HT3 serotonin receptors and nicotinic acetylcholine receptors

Cys-loop receptors are pentameric ligand-gated ion channels that facilitate communication within the nervous system. Upon neurotransmitter binding, these receptors undergo an allosteric activation mechanism connecting the binding event to the membrane-spanning channel pore, which expands to conduct ions. Some of the earliest steps in this activation mechanism are carried out by residues proximal to the binding site, the relative positioning of which may reflect functional differences among members of the Cys-loop family of receptors. Herein, we investigated key side-chain interactions near the binding site via mutagenesis and two-electrode voltage-clamp electrophysiology in serotonin-gated 5-HT3A receptors (5-HT3ARs) and nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus laevis oocytes. We found that a triad of residues aligning to Thr-152, Glu-209, and Lys-211 in the 5-HT3AR can be exchanged between the homomeric 5-HT3AR and the muscle-type nAChR α-subunit with small functional consequences. Via triple mutant cycle analysis, we demonstrated that this triad forms an interdependent network in the muscle-type nAChR. Furthermore, nAChR-type mutations of the 5-HT3AR affect the affinity of nicotine, a competitive antagonist of 5-HT3ARs, in a cooperative manner. Using mutant cycle analyses between the 5-HT3A triad, loop A residues Asn-101 and Glu-102, β9 residue Lys-197, and the channel gate at Thr-257, we observed that residues in this region are energetically linked to the channel gate and are particularly sensitive to mutations that introduce a net positive charge. This study expands our understanding of the differences and similarities in the activation mechanisms of Cys-loop receptors.

In silico, Synthesis and Biological Investigations of Pyrrolo[3,4-C]Pyrrole Hydroxamic Acid Derivatives as Potential Anticancer Agents

Based in a general structural pharmacophore model of suberoylanilide hydroxamic acid (commercially known as Vorinostat©), we synthesized a series of new pyrrolo[3,4-c]pyrrole hydroxamic acid derivatives, 9a-c, to be tested as candidates for anti-cancer drugs. The evaluation of their possible biological activity was assessed in two ways: a) computational characterization from molecular calculations and quantum reactivity descriptors and b) biological assays. Molecular docking and density functional theory calculations were performed to assess the binding properties of our newly synthesized pyrrolo[3,4-c] pyrrole hydroxamic acid derivatives, employing as the biological target the histone deacetylase isoforms available in the protein data bank. Furthermore, to characterize the effect of changing the functional groups that we varied while designing our drug model, and to improve the assessment of the binding energy, conceptual density functional theory reactivity descriptors were calculated to rationalize the capability of the new drugs to interact with the histones active site. Our findings show that the newly synthesized derivative, 9c, display the best energetic coupling with the biological target and the more favorable values of the density functional theory descriptors to interact with the active site. The biological assay of the anti-cancer drug candidates was done using three different techniques: i) anti-proliferative activity on two breast cancer cell lines; ii) Histone H3 acetylation; and iii) DNA damage. Docking studies were performed on histone deacetylase enzymes. The biological function of these enzymes is the deacetylation of histones. We analyze the level of histone acetylation in two cell lines. The computational findings are in good agreement with the biological evaluation. Our main contribution is that one of our newly synthesized derivatives, 9c, performs better than the commercial reference suberoylanilide hydroxamic acid.

One-megadalton metalloenzyme complex in Geobacter metallireducens involved in benzene ring reduction beyond the biological redox window

Reversible biological electron transfer usually occurs between redox couples at standard redox potentials ranging from +0.8 to -0.5 V. Dearomatizing benzoyl-CoA reductases (BCRs), key enzymes of the globally relevant microbial degradation of aromatic compounds at anoxic sites, catalyze a biological Birch reduction beyond the negative limit of this redox window. The structurally characterized BamBC subunits of class II BCRs accomplish benzene ring reduction at an active-site tungsten cofactor; however, the mechanism and components involved in the energetic coupling of endergonic benzene ring reduction have remained hypothetical. We present a 1-MDa, membrane-associated, Bam[(BC)2DEFGHI]2 complex from the anaerobic bacterium Geobacter metallireducens harboring 4 tungsten, 4 zinc, 2 selenocysteines, 6 FAD, and >50 FeS cofactors. The results suggest that class II BCRs catalyze electron transfer to the aromatic ring, yielding a cyclic 1,5-dienoyl-CoA via two flavin-based electron bifurcation events. This work expands our knowledge of energetic couplings in biology by high-molecular-mass electron bifurcating machineries.

Singlet Fission Involves an Interplay between Energetic Driving Force and Electronic Coupling in Perylenediimide Films.

Due to its ability to offset thermalization losses in photoharvesting systems, singlet fission has become a topic of research interest. During singlet fission, a high energy spin-singlet state in an organic semiconductor divides its energy to form two lower energy spin-triplet excitations on neighboring chromophores. While key insights into mechanisms leading to singlet fission have been gained recently, developing photostable compounds that undergo quantitative singlet fission remains a key challenge. In this report, we explore triplet exciton production via singlet fission in films of perylenediimides, a class of compounds with a long history of use as industrial dyes and pigments due to their photostability. As singlet fission necessitates electron transfer between neighboring molecules, its rate and yield depend sensitively on their local arrangement. By adding different functional groups at their imide positions, we control how perylenediimides pack in the solid state. We find inducing a long axis displacement of ∼3 Å between neighboring perylenediimides gives a maximal triplet production yield of 178% with a fission rate of ∼245 ps despite the presence of an activation barrier of ∼190 meV. These findings disagree with Marcus theory predictions for the optimal perylenediimide geometry for singlet fission, but do agree with Redfield theory calculations that allow singlet fission to occur via a charge transfer-mediated superexchange mechanism. Unfortunately, triplets produced by singlet fission are found to decay over tens of nanoseconds. Our results highlight that singlet fission materials must be designed to not only produce triplet excitons but to also facilitate their extraction.

Energy Landscape of the Substrate Translocation Equilibrium of Plasma-Membrane Glutamate Transporters.

Glutamate transporters maintain a large glutamate concentration gradient across synaptic membranes and are, thus, critical for functioning of the excitatory synapse. Mammalian glutamate transporters concentrate glutamate inside cells through energetic coupling of glutamate flux to the transmembrane concentration gradient of Na+. Structural models based on an archeal homologue, GltPh, suggest an elevator-like carrier mechanism. However, the energetic determinants of this carrier-based movement are not well understood. Although electrostatics play an important role in governing these energetics, their implication on transport dynamics has not been studied. Here, we combine a pre-steady-state kinetic analysis of the translocation equilibrium with electrostatic computations to gain insight into the energetics of the translocation process. Our results show the biphasic nature of translocation, consistent with the existence of an intermediate on the translocation pathway. In the absence of voltage, the equilibrium is shifted to the outward-facing configuration. Electrostatic computations confirm the intermediate state and show that the elevator-like movement is energetically feasible in the presence of bound Na+ ions, whereas a substrate-hopping model is energetically prohibitive. Our results highlight the critical contribution of charge compensation to transport and add to results from previous molecular dynamics simulations for improved understanding of the glutamate translocation process.

A Cooperative Folding Unit as the Structural Link for Energetic Coupling within a Protein.

Previously, we demonstrated that binding of a ligand to Escherichia coli cofactor-dependent phosphoglycerate mutase (dPGM), a homodimeric protein, is energetically coupled with dimerization. The equilibrium unfolding of dPGM occurs with a stable, monomeric intermediate. Binding of several nonsubstrate metabolites stabilizes the dimeric native form over the monomeric intermediate, reducing the population of the intermediate. Both the active site and the dimer interface appear to be unfolded in the intermediate. We hypothesized that a loop containing residues 118-152 was responsible for the energetic coupling between the dimer interface and the distal active site and was unfolded in the intermediate. Here, we investigated the structure of the dPGM intermediate by probing side-chain interactions and solvent accessibility of the peptide backbone. By comparing the effect of a mutation on the global stability and the stability of the intermediate, we determine an equilibrium φ value (φeq value), which provides information about whether side-chain interactions are retained or lost in the intermediate. Hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) was used to investigate differences in the solvent accessibility of the peptide backbone in the intermediate and native forms of dPGM. The results of φeq value analysis and HDX-MS reveal the least stable folding unit of dPGM, which is unfolded in the intermediate and links the active site to the dimer interface. The structure of the intermediate reveals how the cooperative network of residues in dPGM gives rise to the observed energetic coupling between dimerization and ligand binding.

Quantifying the Relationship between Single-Molecule Probes and Subunit Rotation in the Ribosome

A major challenge in the study of biomolecular assemblies is to identify reaction coordinates that precisely monitor conformational rearrangements. This is central to the interpretation of single-molecule fluorescence resonance energy transfer measurements, where the observed dynamics depends on the labeling strategy. As an example, different probes of subunit rotation in the ribosome have provided qualitatively distinct descriptions. In one study, changes in fluorescence suggested that the 30S body undergoes a single rotation/back-rotation cycle during the process of mRNA-tRNA translocation. In contrast, an alternate assay implicated the presence of reversible rotation events before completing translocation. For future single-molecule experiments to unambiguously measure the relationship between subunit rotation and translocation, it is necessary to rationalize these conflicting descriptions. To this end, we have simulated hundreds of spontaneous subunit rotation events (≈8°) using a residue-level coarse-grained model of the ribosome. We analyzed nine different reaction coordinates and found that the apparently inconsistent measurements are likely a consequence of ribosomal flexibility. Further, we propose a metric for quantifying the degree of energetic coupling between experimentally measured degrees of freedom and subunit rotation. This analysis provides a physically grounded framework that can guide the development of more precise single-molecule techniques.

A common mechanism for CFTR potentiators.

Cystic fibrosis (CF) is a channelopathy caused by loss-of-function mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a phosphorylation-activated and adenosine triphosphate (ATP)-gated chloride channel. In the past few years, high-throughput drug screening has successfully realized the first US Food and Drug Administration-approved therapy for CF, called ivacaftor (or VX-770). A more recent CFTR potentiator, GLPG1837 (N-(3-carbamoyl-5,5,7,7-tetramethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-2-yl)-1H-pyrazole-3-carboxamide), has been shown to exhibit a higher efficacy than ivacaftor for the G551D mutation, yet the underlying mechanism of GLPG1837 remains unclear. Here we find that despite their differences in potency and efficacy, GLPG1837 and VX-770 potentiate CFTR gating in a remarkably similar manner. Specifically, they share similar effects on single-channel kinetics of wild-type CFTR. Their actions are independent of nucleotide-binding domain (NBD) dimerization and ATP hydrolysis, critical steps controlling CFTR's gate opening and closing, respectively. By applying the two reagents together, we provide evidence that GLPG1837 and VX-770 likely compete for the same site, whereas GLPG1837 and the high-affinity ATP analogue 2'-deoxy-N6-(2-phenylethyl)-adenosine-5'-O-triphosphate (dPATP) work synergistically through two different sites. We also find that the apparent affinity for GLPG1837 is dependent on the open probability of the channel, suggesting a state-dependent binding of the drug to CFTR (higher binding affinity for the open state than the closed state), which is consistent with the classic mechanism for allosteric modulation. We propose a simple four-state kinetic model featuring an energetic coupling between CFTR gating and potentiator binding to explain our experimental results.

NOX4 functions as a mitochondrial energetic sensor coupling cancer metabolic reprogramming to drug resistance

The molecular mechanisms that couple glycolysis to cancer drug resistance remain unclear. Here we identify an ATP-binding motif within the NADPH oxidase isoform, NOX4, and show that ATP directly binds and negatively regulates NOX4 activity. We find that NOX4 localizes to the inner mitochondria membrane and that subcellular redistribution of ATP levels from the mitochondria act as an allosteric switch to activate NOX4. We provide evidence that NOX4-derived reactive oxygen species (ROS) inhibits P300/CBP-associated factor (PCAF)-dependent acetylation and lysosomal degradation of the pyruvate kinase-M2 isoform (PKM2). Finally, we show that NOX4 silencing, through PKM2, sensitizes cultured and ex vivo freshly isolated human-renal carcinoma cells to drug-induced cell death in xenograft models and ex vivo cultures. These findings highlight yet unidentified insights into the molecular events driving cancer evasive resistance and suggest modulation of ATP levels together with cytotoxic drugs could overcome drug-resistance in glycolytic cancers.

Enantiomeric barbiturates bind distinct inter- and intrasubunit binding sites in a nicotinic acetylcholine receptor (nAChR)

Nicotinic acetylcholine receptors (nAChRs) and γ-aminobutyric acid type A receptors (GABAARs) are members of the pentameric ligand-gated ion channel superfamily. Drugs acting as positive allosteric modulators of muscle-type α2βγδ nAChRs, of use in treatment of neuromuscular disorders, have been hard to identify. However, identification of nAChR allosteric modulator binding sites has been facilitated by using drugs developed as photoreactive GABAAR modulators. Recently, R-1-methyl-5-allyl-5-(m-trifluoromethyl-diazirinylphenyl) barbituric acid (R-mTFD-MPAB), an anesthetic and GABAAR potentiator, has been shown to inhibit Torpedo α2βγδ nAChRs, binding in the ion channel and to a γ+-α- subunit interface site similar to its GABAAR intersubunit binding site. In contrast, S-1-methyl-5-propyl-5-(m-trifluoromethyl-diazirinylphenyl) barbituric acid (S-mTFD-MPPB) acts as a convulsant and GABAAR inhibitor. Photolabeling studies established that S-mTFD-MPPB binds to the same GABAAR intersubunit binding site as R-mTFD-MPAB, but with negative rather than positive energetic coupling to GABA binding. We now show that S-mTFD-MPPB binds with the same state (agonist) dependence as R-mTFD-MPAB within the nAChR ion channel, but it does not bind to the intersubunit binding site. Rather, S-mTFD-MPPB binds to intrasubunit sites within the α and δ subunits, photolabeling αVal-218 (αM1), δPhe-232 (δM1), δThr-274 (δM2), and δIle-288 (δM3). Propofol, a general anesthetic that binds to GABAAR intersubunit sites, inhibited [3H]S-mTFD-MPPB photolabeling of these nAChR intrasubunit binding sites. These results demonstrate that in an nAChR, the subtle difference in structure between S-mTFD-MPPB and R-mTFD-MPAB (chirality; 5-propyl versus 5-allyl) determines selectivity for intra- versus intersubunit sites, in contrast to GABAARs, where this difference affects state dependence of binding to a common site.

Dynamics of antipolar distortions

Materials possessing antipolar cation motions are currently receiving a lot of attention because they are fundamentally intriguing while being technologically promising. Most studies devoted to these complex materials have focused on their static properties or on their zone-center phonons. As a result, some important dynamics of antipolar cation distortions, such as the temperature behavior of their phonon frequencies, have been much less investigated, despite the possibility to exhibit unusual features. Here, we report the results and analysis of atomistic simulations revealing and explaining such dynamics for BiFeO3 bulks being subject to hydrostatic pressure. It is first predicted that cooling such material yields the following phase transition sequence: the cubic paraelectric Pmbar 3m state at high temperature, followed by an intermediate phase possessing long-range-ordered in-phase oxygen octahedral tiltings, and then the Pnma state that is known to possess antipolar cation motions in addition to in-phase and antiphase oxygen octahedral tiltings. Antipolar cation modes are found to all have high phonon frequencies that are independent of temperature in the paraelectric phase. On the other hand and in addition to antipolar cation modes increasing in number, some phonons possessing antipolar cation character are rather soft in the intermediate and Pnma states. Analysis of our data combined with the development of a simple model reveals that such features originate from a dynamical mixing between pure antipolar cation phonons and fluctuations of oxygen octahedral tiltings, as a result of a specific trilinear energetic coupling. The developed model can also be easily applied to predict dynamics of antipolar cation motions for other possible structural paths bringing Pmbar 3m to Pnma states.

Revealing extracellular electron transfer mediated parasitism: energetic considerations

Extracellular electron transfer (EET) is a mechanism that allows energetic coupling between two microorganisms or between a microorganism and an electrode surface. EET is either supported by direct physical contacts or mediated by electron shuttles. So far, studies dealing with interspecies EET (so-called IET) have mainly focused on possible syntrophic interactions between microorganisms favoured by this mechanism. In this article, the case of fermentative bacteria receiving extracellular electrons while fermenting a substrate is considered. A thermodynamical analysis based on metabolic energy balances was applied to re-investigate experimental data from the literature. Results suggest that the observations of a decrease of cell biomass yields of fermentative electron-accepting species, as mostly reported, can be unravelled by EET energetics and correspond to parasitism in case of IET. As an illustration, the growth yield decrease of Propionibacterium freudenreichii (−14%) observed in electro-fermentation experiments was fully explained by EET energetics when electrons were used by this species at a potential of −0.12 ± 0.01 V vs SHE. Analysis of other cases showed that, in addition to EET energetics in Clostridium pasteurianum, biological regulations can also be involved in such biomass yield decrease (−33% to −38%). Interestingly, the diminution of bacterial biomass production is always concomitant with an increased production of reduced compounds making IET-mediated parasitism and electro-fermentation attractive ways to optimize carbon fluxes in fermentation processes.