Biomedical subjects

Igor Goychuk

Publications and source records attributed to Igor Goychuk.

12 recordsLinked to original sources

PubMed2006

Quantum stochastic synchronization.

We study, within the spin-boson dynamics, the synchronization of a quantum tunneling system with an external, time-periodic driving signal. As a main result, we find that at a sufficiently large system-bath coupling strength (i.e., for a friction strength alpha > 1) the thermal noise plays a constructive role in yielding forced synchronization. This noise-induced synchronization can occur when the driving frequency is larger than the zero-temperature tunneling rate. As an application evidencing the effect, we consider the charge transfer dynamics in molecular complexes.

Journal Article↗

PubMed2006

Optimal design of microarray immunoassays to compensate for kinetic limitations: theory and experiment.

In this report we examine the limitations of existing microarray immunoassays and investigate how best to optimize them using theoretical and experimental approaches. Derived from DNA technology, microarray immunoassays present a major technological challenge with much greater physicochemical complexity. A key physicochemical limitation of the current generation of microarray immunoassays is a strong dependence of antibody microspot kinetics on the mass flux to the spot as was reported by us previously. In this report we analyze, theoretically and experimentally, the effects of microarray design parameters (incubation vessel geometry, incubation time, stirring, spot size, antibody-binding site density, etc.) on microspot reaction kinetics and sensitivity. Using a two-compartment model, the quantitative descriptors of the microspot reaction were determined for different incubation and microarray design conditions. This analysis revealed profound mass transport limitations in the observed kinetics, which may be slowed down as much as hundreds of times compared with the solution kinetics. The data obtained were considered with relevance to microspot assay diffusional and adsorptive processes, enabling us to validate some of the underlying principles of the antibody microspot reaction mechanism and provide guidelines for optimal microspot immunoassay design. For an assay optimized to maximize the reaction velocity on a spot, we demonstrate sensitivities in the am and low fm ranges for a system containing a representative sample of antigen-antibody pairs. In addition, a separate panel of low abundance cytokines in blood plasma was detected with remarkably high signal-to-noise ratios.

Antigen-Antibody Complex↗

PubMed2006

Kinetics of antigen binding to antibody microspots: strong limitation by mass transport to the surface.

It is well documented that diffusion has generally a strong effect on the binding kinetics in the microtiter plate immunoassays. However, a systematic quantitative experimental evaluation of the microspot kinetics is still missing in the literature. Our work aims at filling this important gap of knowledge on the example of antigen binding to antibody microspots. A mathematical model was derived within the framework of two-compartment model and applied to the quantitative analysis of the experimental data obtained for typical antibody microspot assays. A strong mass-transport dependence of the antigen-antibody microspot kinetics was identified to be one of the main restrictions of this new technology. The binding reactions are slowed down in the microspot immunoassays by several orders of magnitude as compared with the corresponding well-stirred bulk reactions. The task to relax the mass-transport limitations should thus be one of the most important issues in designing the antibody microarrays. These limitations notwithstanding, the detection range of more than five orders of magnitude and the high sensitivity in the low femtomolar range were experimentally achieved in our study, demonstrating thus an enormous potential of this highly capable technology.

Antigen-Antibody Complex↗

PubMed2006

Antibody microarrays: the crucial impact of mass transport on assay kinetics and sensitivity.

Although they are superficially similar to DNA microarrays, immunoassay microarrays represent a daunting technological challenge owing to the much wider diversity of proteins. Yet, as the leading edge of bioscience migrates from genomics to proteomics, the complexity and enormous dynamic range of proteins in a cell necessitate an analytic tool with exceptional specificity and sensitivity. In theory, microspot immunoassays could fulfill this need. However, antibody microarrays have had limited success to date, and have often required a highly sensitive detection system and/or sophisticated immobilization approach to be of any use for the profiling of complex specimens. There is a solid body of work on the theory of microspot reaction kinetics, yet much of the published experimental work on protein microarray development pays insufficient attention to the kinetic aspects of this interaction. This review explains that one of the main limitations for the sensitivity of current generation microspot immunoassays is the strong dependence of antibody microspot kinetics upon mass flux to the spot. This not only involves migration of analyte in solution, but also across the surface of the solid phase. Understanding of this effect will be discussed, along with several related effects and their significance to improving existing microarray designs. It is concluded that current efforts may be too focused on areas that cannot improve performance significantly, and that other critical areas of design should receive more attention. Finally, the review addresses the question of whether ambient analyte immunoassay is truly a separate category of microspot assay, with the conclusion that this may be a flawed concept.

Antibodies↗

PubMed2005

Non-Markovian stochastic resonance: three-state model of ion channel gating.

Stochastic resonance in single voltage-dependent ion channels is investigated within a three-state non-Markovian modeling of the ion channel conformational dynamics. In contrast to a two-state description one assumes the presence of an additional closed state for the ion channel which mimics the manifold of voltage-independent closed subconformations (inactivated "state"). The conformational transition into the open state occurs through a domain of voltage-dependent closed subconformations (closed "state"). At distinct variance with the standard two-state and also the three-state Markovian approach, the inactivated state is characterized by a broad, nonexponential probability distribution of corresponding residence times. The linear response to a periodic voltage signal is determined for arbitrary distributions of the channel's recovery times. Analytical results are obtained for the spectral amplification of the applied signal and the corresponding signal-to-noise ratio. Alternatively, these results are also derived by use of a corresponding two-state non-Markovian theory which is based on driven integral renewal equations [I. Goychuk and P. Hänggi, Phys. Rev. E 69, 021104 (2004)]. The non-Markovian features of stochastic resonance are studied for a power law distribution of the residence time intervals in the inactivated state which exhibits a large variance. A comparison with the case of biexponentially distributed residence times possessing the same mean value, i.e., the simplest non-Markovian two-state description, is also presented.

Cell Membrane↗

PubMed2005

Rate processes with non-Markovian dynamical disorder.

Rate processes with dynamical disorder are investigated within a simple framework provided by unidirectional electron transfer (ET) with fluctuating transfer rate. The rate fluctuations are assumed to be described by a non-Markovian stochastic jump process which reflects conformational dynamics of an electron transferring donor-acceptor molecular complex. A tractable analytical expression is obtained for the relaxation of the donor population (in the Laplace-transformed time domain) averaged over the stationary conformational fluctuations. The corresponding mean transfer time is also obtained in an analytical form. The case of two-state fluctuations is studied in detail for a model incorporating substate diffusion within one of the conformations. It is shown that an increase of the conformational diffusion time results in a gradual transition from the regime of fast modulation characterized by the averaged ET rate to the regime of quasistatic disorder. This transition occurs at the conformational mean residence time intervals fixed much less than the inverse of the corresponding ET rates. An explanation of this paradoxical effect is provided. Moreover, its presence is also manifested for the simplest, exactly solvable non-Markovian model with a biexponential distribution of the residence times in one of the conformations. The nontrivial conditions for this phenomenon to occur are found.

Journal Article↗

PubMed2005

Theory of frequency and phase synchronization in a rocked bistable stochastic system.

We investigate the role of noise in the phenomenon of stochastic synchronization of switching events in a rocked, overdamped bistable potential driven by white Gaussian noise, the archetype description of stochastic resonance. We present an approach to the stochastic counting process of noise-induced switching events: starting from the Markovian dynamics of the nonstationary, continuous particle dynamics, one finds upon contraction onto two states a non-Markovian renewal dynamics. A proper definition of an output discrete phase is given, and the time rate of change of its noise average determines the corresponding output frequency. The phenomenon of noise-assisted phase synchronization is investigated in terms of an effective, instantaneous phase diffusion. The theory is applied to rectangular-shaped rocking signals versus increasing input-noise strengths. In this case, for an appropriate choice of the parameter values, the system exhibits a noise-induced frequency locking accompanied by a very pronounced suppression of the phase diffusion of the output signal. Precise numerical simulations corroborate very favorably our analytical results. The novel theoretical findings are also compared with prior ones.

Action Potentials↗

PubMed2004

Fractional diffusion modeling of ion channel gating.

An anomalous diffusion model for ion channel gating is put forward. This scheme is able to describe nonexponential, power-law-like distributions of residence time intervals in several types of ion channels. Our method presents a generalization of the discrete diffusion model by Millhauser, Salpeter, and Oswald [Proc. Natl. Acad. Sci. U.S.A. 85, 1503 (1988)] to the case of a continuous, anomalous slow conformational diffusion. The corresponding generalization is derived from a continuous-time random walk composed of nearest-neighbor jumps which in the scaling limit results in a fractional diffusion equation. The studied model contains three parameters only: the mean residence time, a characteristic time of conformational diffusion, and the index of subdiffusion. A tractable analytical expression for the characteristic function of the residence time distribution is obtained. In the limiting case of normal diffusion, our prior findings [Proc. Natl. Acad. Sci. U.S.A. 99, 3552 (2002)] are reproduced. Depending on the chosen parameters, the fractional diffusion model exhibits a very rich behavior of the residence time distribution with different characteristic time regimes. Moreover, the corresponding autocorrelation function of conductance fluctuations displays nontrivial power law features. Our theoretical model is in good agreement with experimental data for large conductance potassium ion channels.

Animals↗

PubMed2004

Quantum dynamics with non-Markovian fluctuating parameters.

A stochastic approach to the quantum dynamics randomly modulated in time by a discrete state non-Markovian noise, which possesses an arbitrary nonexponential distribution of the residence times, is developed. The formally exact expression for the Laplace-transformed quantum propagator averaged over the stationary realizations of such N -state non-Markovian noise is obtained. The theory possesses a wide range of applications. It includes some previous Markovian and non-Markovian theories as particular cases. In the context of the stochastic theory of spectral line shape and relaxation, the developed approach presents a non-Markovian generalization of the Kubo-Anderson theory of sudden modulation. In particular, the exact analytical expression is derived for the spectral line shape of optical transitions described by a Kubo oscillator with randomly modulated frequency which undergoes jumplike non-Markovian fluctuations in time.

Journal Article↗

PubMed2004

Theory of non-Markovian stochastic resonance.

We consider a two-state model of non-Markovian stochastic resonance (SR) within the framework of the theory of renewal processes. Residence time intervals are assumed to be mutually independent and characterized by some arbitrary nonexponential residence time distributions which are modulated in time by an externally applied signal. Making use of a stochastic path integral approach we obtain general integral equations governing the evolution of conditional probabilities in the presence of an input signal. These equations generalize earlier integral renewal equations by Cox and others to the case of driving-induced nonstationarity. On the basis of these equations a response theory of two-state renewal processes is formulated beyond the linear response approximation. Moreover, a general expression for the linear response function is derived. The connection of the developed approach with the phenomenological theory of linear response for manifest non-Markovian SR put forward [I. Goychuk and P. Hänggi, Phys. Rev. Lett. 91, 070601 (2003)] is clarified and its range of validity is scrutinized. The theory is then applied to SR in symmetric non-Markovian systems and to the class of single ion channels possessing a fractal kinetics.

Journal Article↗

PubMed2003

Non-Markovian stochastic resonance.

The phenomenological linear response theory of non-Markovian stochastic resonance (SR) is put forward for stationary two-state renewal processes. In terms of a derivation of a non-Markov regression theorem we evaluate the characteristic SR-quantifiers; i.e., the spectral power amplification (SPA) and the signal-to-noise ratio (SNR), respectively. In clear contrast to Markovian-SR, a characteristic benchmark of genuine non-Markovian SR is its distinctive dependence of the SPA and SNR on small (adiabatic) driving frequencies; particularly, the adiabatic SNR becomes strongly suppressed over its Markovian counterpart. This non-Markovian SR-theory is elucidated for a fractal gating dynamics of a potassium ion channel possessing an infinite variance of closed sojourn times.

Journal Article↗

PubMed2002

Ion channel gating: a first-passage time analysis of the Kramers type.

The opening rate of voltage-gated potassium ion channels exhibits a characteristic knee-like turnover where the common exponential voltage dependence changes suddenly into a linear one. An explanation of this puzzling crossover is put forward in terms of a stochastic first passage time analysis. The theory predicts that the exponential voltage dependence correlates with the exponential distribution of closed residence times. This feature occurs at large negative voltages when the channel is predominantly closed. In contrast, the linear part of voltage dependence emerges together with a nonexponential distribution of closed dwelling times with increasing voltage, yielding a large opening rate. Depending on the parameter set, the closed-time distribution displays a power law behavior that extends over several decades.

Diffusion↗