Mitochondria at the Nanoscale: Physics Meets Biology-What Does It Mean for Medicine?

Mitochondria are commonly perceived as "cellular power plants". Intriguingly, power conversion is not their only function. In the first part of this paper, we review the role of mitochondria in the evolution of eukaryotic organisms and in the regulation of the human body, specifically focusing on cancer and autism in relation to mitochondrial dysfunction. In the second part, we overview our previous works, revealing the physical principles of operation for proton-pumping complexes in the inner mitochondrial membrane. Our proposed simple models reveal the physical mechanisms of energy exchange. They can be further expanded to answer open questions about mitochondrial functions and the medical treatment of diseases associated with mitochondrial disorders.

Acoustically Induced Giant Synthetic Hall Voltages in Graphene.

Any departure from graphene's flatness leads to the emergence of artificial gauge fields that act on the motion of the Dirac fermions through an associated pseudomagnetic field. Here, we demonstrate the tunability of strong gauge fields in nonlocal experiments using a large planar graphene sheet that conforms to the deformation of a piezoelectric layer by a surface acoustic wave. The acoustic wave induces a longitudinal and a giant synthetic Hall voltage in the absence of external magnetic fields. The superposition of a synthetic Hall potential and a conventional Hall voltage can annihilate the sample's transverse potential at large external magnetic fields. Surface acoustic waves thus provide a promising and facile avenue for the exploitation of gauge fields in large planar graphene systems.

Cytochrome c oxidase oxygen reduction reaction induced by cytochrome c on nickel-coordination surfaces based on graphene oxide in suspension.

BACKGROUND: The electrochemical and spectroscopic investigation of bacterial electron-transfer proteins stabilized on solid state electrodes has provided an effective approach for functional respiratory enzyme studies. METHODS: We assess the biocompatibility of carboxylated graphene oxide (CGO) functionalized with Nickel nitrilotriacetic groups (CGO-NiNTA) ccordinating His-tagged cytochrome c oxidase (CcO) from Rhodobacter sphaeroides. RESULTS: Kinetic studies employing UV-visible absorption spectroscopy confirmed that the immobilized CcO oxidized horse-heart cytochrome c (Cyt c) albeit at a slower rate than isolated CcO. The oxygen reduction reaction as catalyzed by immobilized CcO could be clearly distinguished from that arising from CGO-NiNTA in the presence of Cyt c and dithiothreitol (DTT) as a sacrificial reducing agent. Our findings indicate that while the protein content is about 3.7‰ by mass with respect to the support, the contribution to the oxygen consumption activity averaged at 56.3%. CONCLUSIONS: The CGO-based support stabilizes the free enzyme which, while capable of Cyt c oxidation, is unable to carry out oxygen consumption in solution on its own under our conditions. The turnover rate for the immobilized CcO was as high as 240 O2 molecules per second per CcO unit. GENERAL SIGNIFICANCE: In vitro investigations of electron flow on isolated components of bacterial electron-transfer enzymes immobilized on the surface of CGO in suspension are expected to shed new light on microbial bioenergetic functions, that could ultimately contribute toward the improvement of performance in living organisms.

Perylene bisbenzimidazole nonlinear dielectric material for energy storage.

A novel perylene bisbenzimidazole comprising both donor and acceptor functional groups was designed, synthesized, and characterized. This structure exhibits potentially useful physical properties, including a nonlinear dielectric response to an increasing electric field. This material can be used in energy storage devices as the dielectric part of a capacitor. Energy storage devices based on film capacitors are targeting applications in a wide range of industrial, residential and transportation systems.

Energy transfer efficiency in the chromophore network strongly coupled to a vibrational mode.

Using methods from condensed matter and statistical physics, we examine the transport of excitons through the photosynthetic complex from a receiving antenna to a reaction center. Writing the equations of motion for the exciton creation-annihilation operators, we are able to describe the exciton dynamics, even in the regime when the reorganization energy is of the order of the intrasystem couplings. We determine the exciton transfer efficiency in the presence of a quenching field and protein environment. While the majority of the protein vibrational modes are treated as a heat bath, we address the situation when specific modes are strongly coupled to excitons and examine the effects of these modes on the energy transfer efficiency in the steady-state regime. Using the structural parameters of the Fenna-Matthews-Olson complex, we find that, for vibrational frequencies below 16 meV, the exciton transfer is drastically suppressed. We attribute this effect to the formation of a "mixed exciton-vibrational mode" where the exciton is transferred back and forth between the two pigments with the absorption or emission of vibrational quanta, instead of proceeding to the reaction center. The same effect suppresses the quantum beating at the vibrational frequency of 25 meV. We also show that the efficiency of the energy transfer can be enhanced when the vibrational mode strongly couples to the third pigment only, instead of coupling to the entire system.

Optimal rates for electron transfer in Marcus theory.

We examine electron transfer between two quantum states in the presence of a dissipative environment represented as a set of independent harmonic oscillators. For this simple model, the Marcus transfer rates can be derived from the equations of motion for electronic operators and we show that these rates are associated to an explicit expression for the environment correlation time. We demonstrate that as a manifestation of the Goldilocks principle, the optimal transfer is governed by a single parameter which is equal to just the inverse square root of 2.

Electrostatic models of electron-driven proton transfer across a lipid membrane.

We present two models for electron-driven uphill proton transport across lipid membranes, with the electron energy converted to the proton gradient via the electrostatic interaction. In the first model, associated with the cytochrome c oxidase complex in the inner mitochondria membranes, the electrostatic coupling to the site occupied by an electron lowers the energy level of the proton-binding site, making proton transfer possible. In the second model, roughly describing the redox loop in a nitrate respiration of E. coli bacteria, an electron displaces a proton from the negative side of the membrane to a shuttle, which subsequently diffuses across the membrane and unloads the proton to its positive side. We show that both models can be described by the same approach, which can be significantly simplified if the system is separated into several clusters, with strong Coulomb interaction inside each cluster and weak transfer couplings between them. We derive and solve the equations of motion for the electron and proton creation/annihilation operators, taking into account the appropriate Coulomb terms, tunnel couplings, and the interaction with the environment. For the second model, these equations of motion are solved jointly with a Langevin-type equation for the shuttle position. We obtain expressions for the electron and proton currents and determine their dependence on the electron and proton voltage build-ups, on-site charging energies, reorganization energies, temperature, and other system parameters. We show that the quantum yield in our models can be up to 100% and the power-conversion efficiency can reach 35%.

Kinetics of proton pumping in cytochrome c oxidase.

We propose a simple model of cytochrome c oxidase, including four redox centers and four protonable sites, to study the time evolution of electrostatically coupled electron and proton transfers initiated by the injection of a single electron into the enzyme. We derive a system of master equations for electron and proton state probabilities and show that an efficient pumping of protons across the membrane can be obtained for a reasonable set of parameters. All four experimentally observed kinetic phases appear naturally from our model. We also calculate the dependence of the pumping efficiency on the transmembrane voltage at different temperatures and discuss a possible mechanism of the redox-driven proton translocation.

Förster mechanism of electron-driven proton pumps.

We examine a simple model of proton pumping through the inner membrane of mitochondria in the living cell. We demonstrate that the pumping process can be described using approaches of condensed matter physics. In the framework of this model, we show that the resonant Förster-type energy exchange due to electron-proton Coulomb interaction can provide a unidirectional flow of protons against an electrochemical proton gradient, thereby accomplishing proton pumping. The dependence of this effect on temperature as well as electron and proton voltage buildups are obtained taking into account electrostatic forces and noise in the environment. We find that the proton pump works with maximum efficiency in the range of temperatures and transmembrane electrochemical potentials which correspond to the parameters of living cells.