Mechanism Of Energy Transduction Research Articles

The 50th anniversary of the European Society for Muscle Research: a journey through half a century of scientific advances.

The European Society for Muscle Research (ESMR) started in 1971 as "European Muscle Club" in a joint initiative of Marcus Schaub, Eduard Jenny and Rudolf Billeter (Zurich), Caspar Rüegg (Heidelberg), Jean Légér (Montpellier), Bernard Swynghedauw (Paris), George Maréchal (Brussels), Gabriel Hamoir (Liège), and Endre Biró (Budapest). Since 1972, local organizers took care of muscle conferences held yearly in different European countries and in Israel in 1987. One of the goals was to establish contacts and collaborations between scientists on both sides of the Iron Curtain. Starting as an informal club, enthusiastically guided by Marcus Schaub as secretary (1971-1995) and later by Ger Stienen (1996-2005), Anders Arner (2006-2017) and Wolfgang Linke (2018-), the ESMR meetings steered international collaborations. The meetings witnessed the remarkable advancement of the insight in skeletal, smooth and cardiac muscle structure and function. In the five decades, the thin and thick filament structure has been resolved to the atomic level, the mechanism of acto-myosin energy transduction and force generation as well as its regulation have been elucidated. The molecular basis of striated and smooth muscle diversity has been found in the existence of multiple protein isoforms. The transcriptional, translational and post-translational regulations which give rise to adaptive responses of muscle tissue have been revealed. Many new players entered the field, such as titin, the ryanodine receptor and several signalling factors. Substantial progress has also been made in the identification of the pathogenesis of many hereditary muscle diseases such as Duchenne MuscularDystrophy and Hypertrophic Cardiac Myopathies.

3D nanofabricated soft microrobots with super-compliant picoforce springs as onboard sensors and actuators.

Microscale organisms and specialized motile cells use protein-based spring-like responsive structures to sense, grasp and move. Rendering this biomechanical transduction functionality in an artificial micromachine for applications in single-cell manipulations is challenging due to the need for a bio-applicable nanoscale spring system with a large and programmable strain response to piconewton-scale forces. Here we present three-dimensional nanofabrication and monolithic integration, based on an acrylic elastomer photoresist, of a magnetic spring system with quantifiable compliance sensitive to 0.5 pN, constructed with customized elasticity and magnetization distributions at the nanoscale. We demonstrate the effective design programmability of these 'picospring' ensembles as energy transduction mechanisms for the integrated construction of customized soft micromachines, with onboard sensing and actuation functions at the single-cell scale for microrobotic grasping and locomotion. The integration of active soft springs into three-dimensional nanofabrication offers an avenue to create biocompatible soft microrobots for non-disruptive interactions with biological entities.

Energy harvesting and inter-floor impact noise control using an optimally tuned hybrid damping system

Impact-loaded floor structures radiate undesired sound waves into adjacent rooms, compromising the acoustic comfort. On the other hand, substantial structural vibrations caused by the impact loading offer a promising energy source for harvesting. Nevertheless, a systematic analytical or numerical investigation of simultaneous inter-floor impact sound transmission control and energy harvesting appears to be missing. Current study describes the conceptual development of a fully coupled 3D analytical model of a dual-functional double-plate floor structure optimized for hybrid regenerative control of inter-floor impact sound transmission. Leveraging multi-mode shunted piezoelectric and Electromagnetic Damper (EMD) energy transduction mechanisms, the model structure is composed of two PZT sandwich plates, which are interlinked through a Nonlinear Vibration Absorber (NVA)-based EMD. The finite Fourier cosine transform and standard normal mode approach are employed to treat the governing acousto-elastic equations. Non-dominated Sorting Genetic Algorithm II is applied to tune the system parameters along Pareto frontiers to target maximum pressure mitigation, maximum energy harvesting, or dual-objective optimization, which hires advantageous features from both configurations for an optimal trade-off between them. Simulations reveal that elasto-acoustic response suppression and energy extraction of the employed stand-alone PZT-based conversion mechanism can be remarkably improved with the adopted optimized hybrid PZT/NVA/EMD-equipped system.

Selenite ameliorates the ATP hydrolysis of mitochondrial F1FO-ATPase by changing the redox state of thiol groups and impairs the ADP phosphorylation

Selenite as an inorganic form of selenium can affect the redox state of mitochondria by modifying the thiol groups of cysteines. The F1FO-ATPase has been identified as a mitochondrial target of this compound. Indeed, the bifunctional mechanism of ATP turnover of F1FO-ATPase was differently modified by selenite. The activity of ATP hydrolysis was stimulated, whereas the ADP phosphorylation was inhibited. We ascertain that a possible new protein adduct identified as seleno-dithiol (-S-Se-S-) mercaptoethanol-sensitive caused the activation of F-ATPase activity and the oxidation of free –SH groups in mitochondria. Conversely, the inhibition of ATP synthesis by selenite might be irreversible. The kinetic analysis of the activation mechanism was an uncompetitive mixed type with respect to the ATP substrate. Selenite bound more selectively to the F1FO-ATPase loaded with the substrate by preferentially forming a tertiary (enzyme-ATP-selenite) complex. Otherwise, the selenite was a competitive mixed-type activator with respect to the Mg2+ cofactor. Thus, selenite more specifically bound to the free enzyme forming the complex enzyme-selenite. However, even if the selenite impaired the catalysis of F1FO-ATPase, the mitochondrial permeability transition pore phenomenon was unaffected. Therefore, the reversible energy transduction mechanism of F1FO-ATPase can be oppositely regulated by selenite.

Phosphorus Chemistry at the Roots of Bioenergetics: Ligand Permutation as the Molecular Basis of the Mechanism of ATP Synthesis/Hydrolysis by FOF1-ATP Synthase.

The integration of phosphorus chemistry with the mechanism of ATP synthesis/hydrolysis requires dynamical information during ATP turnover and catalysis. Oxygen exchange reactions occurring at β-catalytic sites of the FOF1-ATP synthase/F1-ATPase imprint a unique record of molecular events during the catalytic cycle of ATP synthesis/hydrolysis. They have been shown to provide valuable time-resolved information on enzyme catalysis during ATP synthesis and ATP hydrolysis. The present work conducts new experiments on oxygen exchange catalyzed by submitochondrial particles designed to (i) measure the relative rates of Pi-ATP, Pi-HOH, and ATP-HOH isotope exchanges; (ii) probe the effect of ADP removal on the extent of inhibition of the exchanges, and (iii) test their uncoupler sensitivity/resistance. The objectives have been realized based on new experiments on submitochondrial particles, which show that both the Pi-HOH and ATP-HOH exchanges occur at a considerably higher rate relative to the Pi-ATP exchange, an observation that cannot be explained by previous mechanisms. A unifying explanation of the kinetic data that rationalizes these observations is given. The experimental results in (ii) show that ADP removal does not inhibit the intermediate Pi-HOH exchange when ATP and submitochondrial particles are incubated, and that the nucleotide requirement of the intermediate Pi-HOH exchange is adequately met by ATP, but not by ADP. These results contradicts the central postulate in Boyer's binding change mechanism of reversible catalysis at a F1 catalytic site with Keq~1 that predicts an absolute requirement of ADP for the occurrence of the Pi-HOH exchange. The prominent intermediate Pi-HOH exchange occurring under hydrolytic conditions is shown to be best explained by Nath's torsional mechanism of energy transduction and ATP synthesis/hydrolysis, which postulates an essentially irreversible cleavage of ATP by mitochondria/particles, independent from a reversible formation of ATP from ADP and Pi. The explanation within the torsional mechanism is also shown to rationalize the relative insensitivity of the intermediate Pi-HOH exchange to uncouplers observed in the experiments in (iii) compared to the Pi-ATP and ATP-HOH exchanges. This is shown to lead to new concepts and perspectives based on ligand displacement/substitution and ligand permutation for the elucidation of the oxygen exchange reactions within the framework of fundamental phosphorus chemistry. Fast mechanisms that realize the rotation/twist, tilt, permutation and switch of ligands, as well as inversion at the γ-phosphorus synchronously and simultaneously and in a concerted manner, have been proposed, and their stereochemical consequences have been analyzed. These considerations take us beyond the binding change mechanism of ATP synthesis/hydrolysis in bioenergetics.

Elucidating Events within the Black Box of Enzyme Catalysis in Energy Metabolism: Insights into the Molecular Mechanism of ATP Hydrolysis by F1-ATPase.

Oxygen exchange reactions occurring at β-catalytic sites of the FOF1-ATP synthase/F1-ATPase imprint a unique record of molecular events during the catalytic cycle of ATP synthesis/hydrolysis. This work presents a new theory of oxygen exchange and tests it on oxygen exchange data recorded on ATP hydrolysis by mitochondrial F1-ATPase (MF1). The apparent rate constant of oxygen exchange governing the intermediate Pi-HOH exchange accompanying ATP hydrolysis is determined by kinetic analysis over a ~50,000-fold range of substrate ATP concentration (0.1-5000 μM) and a corresponding ~200-fold range of reaction velocity (3.5-650 [moles of Pi/{moles of F1-ATPase}-1 s-1]). Isotopomer distributions of [18O]Pi species containing 0, 1, 2, and 3 labeled oxygen atoms predicted by the theory have been quantified and shown to be in perfect agreement with the experimental distributions over the entire range of medium ATP concentrations without employing adjustable parameters. A novel molecular mechanism of steady-state multisite ATP hydrolysis by the F1-ATPase has been proposed. Our results show that steady-state ATP hydrolysis by F1-ATPase occurs with all three sites occupied by Mg-nucleotide. The various implications arising from models of energy coupling in ATP synthesis/hydrolysis by the ATP synthase/F1-ATPase have been discussed. Current models of ATP hydrolysis by F1-ATPase, including those postulated from single-molecule data, are shown to be effectively bisite models that contradict the data. The trisite catalysis formulated by Nath's torsional mechanism of energy transduction and ATP synthesis/hydrolysis since its first appearance 25 years ago is shown to be in better accord with the experimental record. The total biochemical information on ATP hydrolysis is integrated into a consistent model by the torsional mechanism of ATP synthesis/hydrolysis and shown to elucidate the elementary chemical and mechanical events within the black box of enzyme catalysis in energy metabolism by F1-ATPase.

Ultrafast and Nanoscale Energy Transduction Mechanisms and Coupled Thermal Transport across Interfaces.

The coupled interactions among the fundamental carriers of charge, heat, and electromagnetic fields at interfaces and boundaries give rise to energetic processes that enable a wide array of technologies. The energy transduction among these coupled carriers results in thermal dissipation at these surfaces, often quantified by the thermal boundary resistance, thus driving the functionalities of the modern nanotechnologies that are continuing to provide transformational benefits in computing, communication, health care, clean energy, power recycling, sensing, and manufacturing, to name a few. It is the purpose of this Review to summarize recent works that have been reported on ultrafast and nanoscale energy transduction and heat transfer mechanisms across interfaces when different thermal carriers couple near or across interfaces. We review coupled heat transfer mechanisms at interfaces of solids, liquids, gasses, and plasmas that drive the resulting interfacial heat transfer and temperature gradients due to energy and momentum coupling among various combinations of electrons, vibrons, photons, polaritons (plasmon polaritons and phonon polaritons), and molecules. These interfacial thermal transport processes with coupled energy carriers involve relatively recent research, and thus, several opportunities exist to further develop these nascent fields, which we comment on throughout the course of this Review.

Beyond binding change: the molecular mechanism of ATP hydrolysis by F1-ATPase and its biochemical consequences.

F1-ATPase is a universal multisubunit enzyme and the smallest-known motor that, fueled by the process of ATP hydrolysis, rotates in 120o steps. A central question is how the elementary chemical steps occurring in the three catalytic sites are coupled to the mechanical rotation. Here, we performed cold chase promotion experiments and measured the rates and extents of hydrolysis of preloaded bound ATP and promoter ATP bound in the catalytic sites. We found that rotation was caused by the electrostatic free energy change associated with the ATP cleavage reaction followed by Pi release. The combination of these two processes occurs sequentially in two different catalytic sites on the enzyme, thereby driving the two rotational sub-steps of the 120o rotation. The mechanistic implications of this finding are discussed based on the overall energy balance of the system. General principles of free energy transduction are formulated, and their important physical and biochemical consequences are analyzed. In particular, how exactly ATP performs useful external work in biomolecular systems is discussed. A molecular mechanism of steady-state, trisite ATP hydrolysis by F1-ATPase, consistent with physical laws and principles and the consolidated body of available biochemical information, is developed. Taken together with previous results, this mechanism essentially completes the coupling scheme. Discrete snapshots seen in high-resolution X-ray structures are assigned to specific intermediate stages in the 120o hydrolysis cycle, and reasons for the necessity of these conformations are readily understood. The major roles played by the "minor" subunits of ATP synthase in enabling physiological energy coupling and catalysis, first predicted by Nath's torsional mechanism of energy transduction and ATP synthesis 25 years ago, are now revealed with great clarity. The working of nine-stepped (bMF1, hMF1), six-stepped (TF1, EF1), and three-stepped (PdF1) F1 motors and of the α3β3γ subcomplex of F1 is explained by the same unified mechanism without invoking additional assumptions or postulating different mechanochemical coupling schemes. Some novel predictions of the unified theory on the mode of action of F1 inhibitors, such as sodium azide, of great pharmaceutical importance, and on more exotic artificial or hybrid/chimera F1 motors have been made and analyzed mathematically. The detailed ATP hydrolysis cycle for the enzyme as a whole is shown to provide a biochemical basis for a theory of "unisite" and steady-state multisite catalysis by F1-ATPase that had remained elusive for a very long time. The theory is supported by a probability-based calculation of enzyme species distributions and analysis of catalytic site occupancies by Mg-nucleotides and the activity of F1-ATPase. A new concept of energy coupling in ATP synthesis/hydrolysis based on fundamental ligand substitution chemistry has been advanced, which offers a deeper understanding, elucidates enzyme activation and catalysis in a better way, and provides a unified molecular explanation of elementary chemical events occurring at enzyme catalytic sites. As such, these developments take us beyond binding change mechanisms of ATP synthesis/hydrolysis proposed for oxidative phosphorylation and photophosphorylation in bioenergetics.

Mechanisms of Energy Transduction in Mitochondria

Mitochondria play a key role in providing energy for cellular functions, and on the other hand, they are a target, decoder and switch of intracellular signals, generator of secondary messengers and pro-apoptotic factors. Modern ideas about the mechanisms of energy transduction in the mitochondrial membrane were formed after Peter Mitchell created the chemiosmotic theory of ATP synthesis. The data presented in the article can serve as a fundamental basis for further study of the brain in normal and pathological conditions with further extrapolation of the obtained data to humans. Mitochondria play a key role in providing energy for cellular functions, and on the other hand, they are a target, decoder and switch of intracellular signals, generator of secondary messengers and pro-apoptotic factors [1]. Modern ideas about the mechanisms of energy transduction in the mitochondrial membrane were formed after Peter Mitchell created the chemiosmotic theory of ATP synthesis. The energy resources used by the inner mitochondrial membrane are initially directed at the transport of the conjugating proton through the membrane to an area with a higher concentration (energization of the membrane), then the proton gradient is used by the mitochondria as a driving force capable of leading to the synthesis of ATP. Isolation of mitochondrial proteins by D.E. Green and co-workers led to the formation of the idea of “complexes” of the respiratory chain [2].

Energy Harvesting Technologies and Devices from Vehicular Transit and Natural Sources on Roads for a Sustainable Transport: State-of-the-Art Analysis and Commercial Solutions

The roads we travel daily are exposed to several energy sources (mechanical load, solar radiation, heat, air movement, etc.), which can be exploited to make common systems and apparatus for roadways (i.e., lighting, video surveillance, and traffic monitoring systems) energetically autonomous. For decades, research groups have developed many technologies able to scavenge energy from the said sources related to roadways: electromagnetism, piezoelectric and triboelectric harvesters for the cars’ stress and vibrations, photovoltaic modules for sunlight, thermoelectric solutions and pyroelectric materials for heat and wind turbines optimized for low-speed winds, such as the ones produced by moving vehicles. Thus, this paper explores the existing technologies for scavenging energy from sources available on roadways, both natural and related to vehicular transit. At first, to contextualize them within the application scenario, the available energy sources and transduction mechanisms were identified and described, arguing the main requirements that must be considered for developing harvesters applicable on roadways. Afterward, an overview of energy harvesting solutions presented in the scientific literature to recover energy from roadways is introduced, classifying them according to the transduction method (i.e., piezoelectric, triboelectric, electromagnetic, photovoltaic, etc.) and proposed system architecture. Later, a survey of commercial systems available on the market for scavenging energy from roadways is introduced, focusing on their architecture, performance, and installation methods. Lastly, comparative analyses are offered for each device category (i.e., scientific works and commercial products), providing insights to identify the most promising solutions and technologies for developing future self-sustainable smart roads.

Non-Faradaic Electrochemical Energy Transduction Using Catalytic Motors

Mechanical energy generated by self-powered catalytic motors encourages researchers to explore whether their dynamics can be harnessed in developing inexpensive and efficient energy transduction and storage platforms. Herein, we present a non-Faradaic electrochemical energy transduction strategy using buoyancy-driven self-propelled catalytic motors within an electrochemical setup containing a fluorinated tin oxide working electrode and a sustained salt gradient. During propulsion, the motors facilitated advective transfer of ions from the bottom of the fuel solution to the electrode and subsequent formation of an electric double layer capacitor (EDLC) over it. The magnitude of EDLC charging was estimated using open circuit potential (OCP) measurements, which was found to increase with the number of motors in solution. We also observed instantaneous potential spikes over the OCP signal profile, when a motor struck the electrode surface, the frequency of which gets enhanced with the increase in motor speed through the solution. We quantify the OCP generated as a function of number of motors and composition of the fuel solution and also offer an explanation of the energy transduction mechanism in the system. It is expected that catalytic motor-assisted non-Faradaic energy generation will establish itself as an important energy harvesting pathway and when miniaturized, will open up avenues for fabricating autonomous power sources for smart sensors and other devices.

Cryo-EM structures define ubiquinone-10 binding to mitochondrial complex I and conformational transitions accompanying Q-site occupancy

Mitochondrial complex I is a central metabolic enzyme that uses the reducing potential of NADH to reduce ubiquinone-10 (Q10) and drive four protons across the inner mitochondrial membrane, powering oxidative phosphorylation. Although many complex I structures are now available, the mechanisms of Q10 reduction and energy transduction remain controversial. Here, we reconstitute mammalian complex I into phospholipid nanodiscs with exogenous Q10. Using cryo-EM, we reveal a Q10 molecule occupying the full length of the Q-binding site in the ‘active’ (ready-to-go) resting state together with a matching substrate-free structure, and apply molecular dynamics simulations to propose how the charge states of key residues influence the Q10 binding pose. By comparing ligand-bound and ligand-free forms of the ‘deactive’ resting state (that require reactivating to catalyse), we begin to define how substrate binding restructures the deactive Q-binding site, providing insights into its physiological and mechanistic relevance.

Langmuir-Blodgett Graphene-Based Films for Algal Biophotovoltaic Fuel Cells.

The prevalence of photosynthesis, as the major natural solar energy transduction mechanism or biophotovoltaics (BPV), has always intrigued mankind. Over the last decades, we have learned to extract this renewable energy through continuously improving solid-state semiconductive devices, such as the photovoltaic solar cell. Direct utilization of plant-based BPVs has, however, been almost impracticable so far. Nevertheless, the electrochemical platform of fuel cells (FCs) relying on redox potentials of algae suspensions or biofilms on functionalized anode materials has in recent years increasingly been demonstrated to produce clean or carbon-negative electrical power generators. Interestingly, these algal BPVs offer unparalleled advantages, including carbon sequestration, bioremediation and biomass harvesting, while producing electricity. The development of high performance and durable BPVs is dependent on upgraded anode materials with electrochemically dynamic nanostructures. However, the current challenges in the optimization of anode materials remain significant barriers towards the development of commercially viable technology. In this context, two-dimensional (2D) graphene-based carbonaceous material has widely been exploited in such FCs due to its flexible surface functionalization properties. Attempts to economically improve power outputs have, however, been futile owing to molecular scale disorders that limit efficient charge coupling for maximum power generation within the anodic films. Recently, Langmuir–Blodgett (LB) film has been substantiated as an efficacious film-forming technique to tackle the above limitations of algal BPVs; however, the aforesaid technology remains vastly untapped in BPVs. An in-depth electromechanistic view of the fabrication of LB films and their electron transference mechanisms is of huge significance for the scalability of BPVs. However, an inclusive review of LB films applicable to BPVs has yet to be undertaken, prohibiting futuristic applications. Consequently, we report an inclusive description of a contextual outline, functional principles, the LB film-formation mechanism, recent endeavors in developing LB films and acute encounters with prevailing BPV anode materials. Furthermore, the research and scale-up challenges relating to LB film-integrated BPVs are presented along with innovative perceptions of how to improve their practicability in scale-up processes.

Cryo-electron microscopy reveals how acetogenins inhibit mitochondrial respiratory complex I

Mitochondrial complex I (NADH:ubiquinone oxidoreductase), a crucial enzyme in energy metabolism, captures the redox potential energy from NADH oxidation/ubiquinone reduction to create the proton motive force used to drive ATP synthesis in oxidative phosphorylation. High-resolution single-particle electron cryo-EM analyses have provided detailed structural knowledge of the catalytic machinery of complex I, but not of the molecular principles of its energy transduction mechanism. Although ubiquinone is considered to bind in a long channel at the interface of the membrane-embedded and hydrophilic domains, with channel residues likely involved in coupling substrate reduction to proton translocation, no structures with the channel fully occupied have yet been described. Here, we report the structure (determined by cryo-EM) of mouse complex I with a tight-binding natural product acetogenin inhibitor, which resembles the native substrate, bound along the full length of the expected ubiquinone-binding channel. Our structure reveals the mode of acetogenin binding and the molecular basis for structure–activity relationships within the acetogenin family. It also shows that acetogenins are such potent inhibitors because they are highly hydrophobic molecules that contain two specific hydrophilic moieties spaced to lock into two hydrophilic regions of the otherwise hydrophobic channel. The central hydrophilic section of the channel does not favor binding of the isoprenoid chain when the native substrate is fully bound but stabilizes the ubiquinone/ubiquinol headgroup as it transits to/from the active site. Therefore, the amphipathic nature of the channel supports both tight binding of the amphipathic inhibitor and rapid exchange of the ubiquinone/ubiquinol substrate and product.

Structural Basis of Zika Virus Helicase in RNA Unwinding and ATP Hydrolysis.

The flavivirus nonstructural protein 3 helicase (NS3hel) is a multifunctional domain protein that is associated with DNA/RNA helicase, nucleoside triphosphatase (NTPase), and RNA 5'-triphosphatase (RTPase) activities. As an NTPase-dependent superfamily 2 (SF2) member, NS3hel employs an NTP-driven motor force to unwind double-stranded RNA while translocating along single-stranded RNA and is extensively involved in the viral replication process. Although the structures of SF2 helicases are widely investigated as promising drug targets, the mechanism of energy transduction between NTP hydrolysis and the RNA binding sites in ZIKV NS3hel remains elusive. Here, we report the crystal structure of ZIKV NS3hel in complex with its natural substrates ATP-Mn2+ and ssRNA. Distinct from other members of the Flavivirus genus, ssRNA binding to ZIKV NS3hel induces relocation of the active water molecules and ATP-associated metal ions in the NTP hydrolysis active site, which promotes the hydrolysis of ATP and the production of AMP. Our findings highlight the importance of the allosteric role of ssRNA on the modulation of ATP hydrolysis and energy utilization.

Functional Dynamics of an Ancient Membrane-Bound Hydrogenase.

The membrane-bound hydrogenase (Mbh) is a redox-driven Na+/H+ transporter that employs the energy from hydrogen gas (H2) production to catalyze proton pumping and Na+/H+ exchange across cytoplasmic membranes of archaea. Despite a recently resolved structure of this ancient energy-transducing enzyme [Yu et al. Cell2018, 173, 1636–1649], the molecular principles of its redox-driven ion-transport mechanism remain puzzling and of major interest for understanding bioenergetic principles of early cells. Here we use atomistic molecular dynamics (MD) simulations in combination with data clustering methods and quantum chemical calculations to probe principles underlying proton reduction as well as proton and sodium transport in Mbh from the hyperthermophilic archaeon Pyrococcus furiosus. We identify putative Na+ binding sites and proton pathways leading across the membrane and to the NiFe-active center as well as conformational changes that regulate ion uptake. We suggest that Na+ binding and protonation changes at a putative ion-binding site couple to proton transfer across the antiporter-like MbhH subunit by modulating the conformational state of a conserved ion pair at the subunit interface. Our findings illustrate conserved coupling principles within the complex I superfamily and provide functional insight into archaeal energy transduction mechanisms.

Topological wave energy harvesting in bistable lattices

In this paper, we present an input-independent energy harvesting mechanism exploiting topological solitary waves. This class of medium transforming solitons, or transition waves, entails energy radiation in the form of trailing phonons in discrete bistable lattices. We observe numerically and experimentally that the most dominant frequencies of these phonons are invariant to the input excitations as long as transition waves are generated. The phonon energy at each unit cell is clustered around a single invariant frequency, enabling input-independent resonant harvesting with conventional energy transduction mechanisms. The presented mechanism fundamentally breaks the link between the unit cell size and the metamaterial’s operating frequencies, offering a broadband solution to energy harvesting that is particularly robust for low-frequency input sources. We further investigate the effect of lattice discreteness on the energy harvesting potential, observing two performance gaps and a topological wave harvesting pass band where the potential for energy conversion increases almost monotonically. The observed frequency-invariant phonons are intrinsic to the discrete bistable lattices, enabling broadband energy harvesting to be an inherent metamaterial property.

Recent insights into the relative timing of myosin's powerstroke and release of phosphate.

Myosin is a motor enzyme that converts the chemical energy in ATP into mechanical work to drive a myriad of intracellular processes, from muscle contraction to vesicular transport. Key steps in the transduction of energy are the force-generating powerstroke, and the release of phosphate (Pi ) from the nucleotide-binding site. Both events occur rapidly after binding to actin, making it difficult to determine which event occurs first. Early efforts suggested that these events occur simultaneously; however, recent findings indicate that they are separate and distinct events that occur at different rates. High-resolution crystal structures of myosin captured in intermediate states of the ATPase cycle suggest that when Pi is in the active site it prevents the powerstroke from occurring, leading to the hypothesis that Pi -release precedes the powerstroke. However, advances in functional assays, enabling sub-millisecond temporal and nanometer spatial resolution, are challenging this hypothesis. For example, Föster Resonance Energy Transfer (FRET) based assays, as well as single molecule laser trap assays, suggest the opposite; that the powerstroke occurs prior to the release of Pi from myosin's active site. This review provides some historical context and then highlights recent reports that reveal exciting new insight into this fundamental mechanism of energy transduction by this prototypical motor enzyme.

Charge transfer across biomembranes: A solution to the conundrum of high desolvation free energy penalty in ion transport

Charge transfer across membranes is an important problem in a wide variety of fundamental physicochemical and biological processes. Since Mitchell's concept of the ion well advanced in 1968, several models of ion translocation across biomembranes, for instance through the membrane-bound FO portion of ATP synthase have been proposed. None of these models has considered the large desolvation free energy penalty of ~500 meV incurred in transferring a protonic charge from the aqueous phase into the membrane that hinders such charge transfer processes. The difficulty has been pointed out repeatedly. However, the problem of how the adverse ∆Gdesolvation barrier is overcome in order to enable rapid ion translocation in biomembranes has not been satisfactorily resolved. Hence the fact that the self-energy of the charges has been overlooked can be regarded as a main source of confusion in the field of bioenergetics. Further, in order to consider charges of a finite size (and not just point charges), the free energy of transferring the ions from water into a membrane phase of lower dielectric εm needs to be evaluated. Here a solution to the longstanding conundrum has been proposed by including the bound anion – the second ion in Nath's two-ion theory of energy coupling and ATP synthesis − in the free energy calculations. The mechanistic importance of the H+ − A− charge pair in causing rotation and ATP synthesis by ion-protein interactions is highlighted. The ∆G calculations have been performed by using the Kirkwood-Tanford-Warshel (KTW) theory that takes into account the self-energies of the ions. The results show that the adverse ∆Gdesolvation can be almost exactly compensated by the sum of the electrostatic free energy of the charge-charge interactions and the dipole solvation energy for long-range ion pairs. Results of free energy compensation using the KTW theory have been compared with experimental data on the ∆G of ion pairs and shown to be in reasonable agreement. A general thermodynamic cycle for coupled ion transfer has been constructed to further elucidate facilitated ion permeation between water and membrane phases. Molecular interpretations of the results and their implications for various mechanisms of energy transduction have been discussed. We firmly believe that use of electrostatic theories such as the KTW theory that properly include the desolvation free energy penalty arising from the self-energy of the relevant ions are crucial for quantifying charge transfer processes in bioenergetics. Finally, the clear-cut implication is that proton-only and single-ion theories of ATP synthesis, such as the chemiosmotic theory, are grossly inadequate to comprehend energy storage and transduction in biological processes.

Mechanisms of Energy Transduction by Charge Translocating Membrane Proteins.

Life relies on the constant exchange of different forms of energy, i.e., on energy transduction. Therefore, organisms have evolved in a way to be able to harvest the energy made available by external sources (such as light or chemical compounds) and convert these into biological useable energy forms, such as the transmembrane difference of electrochemical potential (Δμ̃). Membrane proteins contribute to the establishment of Δμ̃ by coupling exergonic catalytic reactions to the translocation of charges (electrons/ions) across the membrane. Irrespectively of the energy source and consequent type of reaction, all charge-translocating proteins follow two molecular coupling mechanisms: direct- or indirect-coupling, depending on whether the translocated charge is involved in the driving reaction. In this review, we explore these two coupling mechanisms by thoroughly examining the different types of charge-translocating membrane proteins. For each protein, we analyze the respective reaction thermodynamics, electron transfer/catalytic processes, charge-translocating pathways, and ion/substrate stoichiometries.