Eleonora Alfinito

A network model to correlate conformational change and the impedance spectrum of single proteins

One of the main trend in to date research and development is the miniaturization of electronic devices. In this perspective, integrated nanodevices based on proteins or biomolecules are attracting a major interest. In fact, it has been shown that proteins like bacteriorhodopsin and azurin, manifest electrical properties which are promising for the development of active components in the field of molecular electronics. Here we focus on two relevant kinds of proteins: The bovine rhodopsin, prototype of GPCR protein, and the enzyme acetylcholinesterase (AChE), whose inhibition is one of the most qualified treatments of Alzheimer disease. Both these proteins exert their functioning starting with a conformational change of their native structure. Our guess is that such a change should be accompanied with a detectable variation of their electrical properties. To investigate this conjecture, we present an impedance network model of proteins, able to estimate the different electrical response associated with the different configurations. The model resolution of the electrical response is found able to monitor the structure and the conformational change of the given protein. In this respect, rhodopsin exhibits a better differential response than AChE. This result gives room to different interpretations of the degree of conformational change and in particular supports a recent hypothesis on the existence of a mixed state already in the native configuration of the protein.

Resistance and Resistance Fluctuations in Random Resistor Networks Under Biased Percolation

We consider a two-dimensional random resistor network (RRN) in the presence of two competing biased processes consisting of the breaking and recovering of elementary resistors. These two processes are driven by the joint effects of an electrical bias and of the heat exchange with a thermal bath. The electrical bias is set up by applying a constant voltage or, alternatively, a constant current. Monte Carlo simulations are performed to analyze the network evolution in the full range of bias values. Depending on the bias strength, electrical failure or steady state are achieved. Here we investigate the steady state of the RRN focusing on the properties of the non-Ohmic regime. In constant-voltage conditions, a scaling relation is found between /(0) and V/V(0), where is the average network resistance, (0) the linear regime resistance, and V0 the threshold value for the onset of nonlinearity. A similar relation is found in constant-current conditions. The relative variance of resistance fluctuations also exhibits a strong nonlinearity whose properties are investigated. The power spectral density of resistance fluctuations presents a Lorentzian spectrum and the amplitude of fluctuations shows a significant non-Gaussian behavior in the prebreakdown region. These results compare well with electrical breakdown measurements in thin films of composites and of other conducting materials.

Charge transport in bacteriorhodopsin monolayers : The contribution of conformational change to current-voltage characteristics

When moving from native to light-activated bacteriorhodospin, modification of charge transport consisting of an increase of conductance is correlated to the protein conformational change. A theoretical model based on a map of the protein tertiary structure into a resistor network is implemented to account for a sequential tunneling mechanism of charge transfer through neighbouring amino acids. The model is validated by comparison with current-voltage experiments. The predictability of the model is further tested on bovine rhodopsin, a G-protein coupled receptor (GPCR) also sensitive to light. In this case, results show an opposite behaviour with a decrease of conductance in the presence of light.

ERRATA: FORMATION AND LIFE-TIME OF MEMORY DOMAINS IN THE DISSIPATIVE QUANTUM MODEL OF BRAIN

We show that in the dissipative quantum model of brain the time-dependence of the frequencies of the electrical dipole wave quanta leads to the dynamical organization of the memories in space (i.e., to their localization in more or less diffused regions of the brain) and in time (i.e., to their longer or shorter life-time). The life-time and the localization in domains of the memory states also depend on internal parameters and on the number of links that the brain establishes with the external world. These results agree with the physiological observations of the dynamic formation of neural circuitry which grows as brain develops and relates to external world.

THE DECOHERENCE CRITERION

The decoherence mechanism signals the limits beyond which the system dynamics approaches the classical behavior. We show that in some cases decoherence may also signal the limits beyond which the system dynamics has to be described by quantum field theory, rather than by quantum mechanics.

Non-Gaussian resistance noise near electrical breakdown in granular materials

The distribution of resistance fluctuations of conducting thin films with granular structure near electrical breakdown is studied by numerical simulations. The film is modeled as a resistor network in a steady state determined by the competition between two biased processes, breaking and recovery. Systems of different sizes and with different levels of internal disorder are considered. Sharp deviations from a Gaussian distribution are found near breakdown and the effect increases with the degree of internal disorder. We show that in general this non-Gaussianity is related to the finite size of the system and vanishes in the large size limit. Nevertheless, near the critical point of the conductor–insulator transition, deviations from Gaussianity persist when the size is increased and the distribution of resistance fluctuations is well fitted by the universal Bramwell–Holdsworth–Pinton distribution.

Non-Gaussianity of resistance fluctuations near electrical breakdown

We study the resistance fluctuation distribution of a thin film near electrical breakdown. The film is modelled as a stationary resistor network under biased percolation. Depending on the value of the external current, on the system sizes and on the level of internal disorder, the fluctuation distribution can exhibit a non-Gaussian behaviour. We analyse this non-Gaussianity in terms of the generalized Gumbel distribution recently introduced in the context of highly correlated systems near criticality. We find that when the average fraction of defects approaches the random percolation threshold, the resistance fluctuation distribution is well described by the universal behaviour of the Bramwell–Holdsworth–Pinton distribution.

Topological change and impedance spectrum of rat olfactory receptor I7: A comparative analysis with bovine rhodopsin and bacteriorhodopsin

We present a theoretical investigation on possible selection of olfactory receptors (ORs) as sensing components of nanobiosensors. Accordingly, we generate the impedance spectra of the rat OR I7 in the native and activated states and analyze their differences. In this way, we connect the protein morphological transformation, caused by the sensing action, with its change in electrical impedance. The results are compared with those obtained by studying the best known protein of the G protein coupled receptor (GPCR) family: bovine rhodopsin. Our investigations indicate that a change in morphology goes with a change in impedance spectrum mostly associated with a decrease in the static impedance up to about 60% of the initial value, in qualitative agreement with existing experiments on rat OR I7. The predictiveness of the model is tested successfully for the case of recent experiments on bacteriorhodopsin. The present results point to a promising development of a new class of nanobiosensors based on the electr...

Opsin vs opsin: new materials for biotechnological applications

The need of new diagnostic methods satisfying, as an early detection, a low invasive procedure and a cost-efficient value, is orienting the technological research toward the use of bio-integrated devices, in particular, bio-sensors. The set of know-why necessary to achieve this goal is wide, from biochemistry to electronics and is summarized in an emerging branch of electronics, called proteotronics. Proteotronics is here applied to state a comparative analysis of the electrical responses coming from type-1 and type-2 opsins. In particular, the procedure is used as an early investigation of a recently discovered family of opsins, the proteorhodopsins activated by blue light, BPRs. The results reveal some interesting and unexpected similarities between proteins of the two families, suggesting the global electrical response are not strictly linked to the class identity.The need of new diagnostic methods satisfying, as an early detection, a low invasive procedure and a cost-efficient value, is orienting the technological research toward the use of bio-integrated devices, in particular bio-sensors. The set of know-why necessary to achieve this goal is wide, from biochemistry to electronics and is summarized in an emerging branch of electronics, called \textit{proteotronics}. Proteotronics is here here applied to state a comparative analysis of the electrical responses coming from type-1 and type-2 opsins. In particular, the procedure is used as an early investigation of a recently discovered family of opsins, the proteorhodopsins activated by blue light, BPRs. The results reveal some interesting and unexpected similarities between proteins of the two families, suggesting the global electrical response are not strictly linked to the class identity.

Human olfactory receptor 17-40 as an active part of a nanobiosensor: a microscopic investigation of its electrical properties

Increasing attention has recently been devoted to protein-based nanobiosensors. The main reason is the huge number of possible technological applications, ranging from drug detection to early cancer diagnosis. Their operating model is based on protein activation and the corresponding conformational change due to the capture of an external molecule, the so-called ligand. Recent measurements, performed with different techniques on the human 17-40 olfactory receptor, revealed a very narrow window of response in respect to the odour concentration. This is a crucial point for understanding whether the use of this olfactory receptor as a sensitive part of a nanobiosensor is a good choice. In this paper we investigate the topological and electrical properties of the human olfactory receptor 17-40 with the objective of providing a microscopic interpretation of available experiments. To this purpose, we model the protein by means of a graph that is able to capture the mean features of the 3D backbone structure. The graph is then associated with an equivalent impedance network, able to evaluate the impedance spectra of the olfactory receptor in its native and activated state. We assume a topological origin of the different protein electrical responses to different ligand concentrations: In this perspective all the experimental data are collected and interpreted satisfactorily within a unified scheme, also useful for application to other proteins.