Biomedical subjects

Michael E Fisher

Publications and source records attributed to Michael E Fisher.

18 recordsLinked to original sources

PubMed2007

Molecular motors: a theorist's perspective.

Individual molecular motors, or motor proteins, are enzymatic molecules that convert chemical energy, typically obtained from the hydrolysis of ATP (adenosine triphosphate), into mechanical work and motion. Processive motor proteins, such as kinesin, dynein, and certain myosins, step unidirectionally along linear tracks, specifically microtubules and actin filaments, and play a crucial role in cellular transport processes, organization, and function. In this review some theoretical aspects of motor-protein dynamics are presented in the light of current experimental methods that enable the measurement of the biochemical and biomechanical properties on a single-molecule basis. After a brief discussion of continuum ratchet concepts, we focus on discrete kinetic and stochastic models that yield predictions for the mean velocity, V(F, [ATP], ...), and other observables as a function of an imposed load force F, the ATP concentration, and other variables. The combination of appropriate theory with single-molecule observations should help uncover the mechanisms underlying motor-protein function.

Models, Biological↗

PubMed2006

Static and dynamic critical behavior of a symmetrical binary fluid: a computer simulation.

A symmetrical binary, A+B Lennard-Jones mixture is studied by a combination of semi-grand-canonical Monte Carlo (SGMC) and molecular dynamics (MD) methods near a liquid-liquid critical temperature T(c). Choosing equal chemical potentials for the two species, the SGMC switches identities (A-->B-->A) to generate well-equilibrated configurations of the system on the coexistence curve for T T(c). A finite-size scaling analysis of the concentration susceptibility above T(c) and of the order parameter below T(c) is performed, varying the number of particles from N=400 to 12 800. The data are fully compatible with the expected critical exponents of the three-dimensional Ising universality class. The equilibrium configurations from the SGMC runs are used as initial states for microcanonical MD runs, from which transport coefficients are extracted. Self-diffusion coefficients are obtained from the Einstein relation, while the interdiffusion coefficient and the shear viscosity are estimated from Green-Kubo expressions. As expected, the self-diffusion constant does not display a detectable critical anomaly. With appropriate finite-size scaling analysis, we show that the simulation data for the shear viscosity and the mutual diffusion constant are quite consistent both with the theoretically predicted behavior, including the critical exponents and amplitudes, and with the most accurate experimental evidence.

Journal Article↗

PubMed2006

Critical dynamics in a binary fluid: simulations and finite-size scaling.

We report comprehensive simulations of the critical dynamics of a symmetric binary Lennard-Jones mixture near its consolute point. The self-diffusion coefficient exhibits no detectable anomaly. The data for the shear viscosity and the mutual-diffusion coefficient are fully consistent with the asymptotic power laws and amplitudes predicted by renormalization-group and mode-coupling theories provided finite-size effects and the background contribution to the relevant Onsager coefficient are suitably accounted for. This resolves a controversy raised by recent molecular simulations.

Journal Article↗

PubMed2005

Universality of ionic criticality: size- and charge-asymmetric electrolytes.

Grand-canonical simulations designed to resolve critical universality classes are reported for z:1 hard-core electrolyte models with diameter ratios lambda=a+/a- less than or approximately equal 6. For z=1 Ising-type behavior prevails. Unbiased estimates of Tc(lambda) are within 1% of previous (biased) estimates but the critical densities are approximately 5% lower. Ising character is also established for the 2:1 and 3:1 equisized models, along with critical amplitudes and improved Tc estimates. For z=3, however, strong finite-size effects reduce the confidence level although classical and O (n>or=3) criticality are excluded.

Journal Article↗

PubMed2005

Kinesin crouches to sprint but resists pushing.

Recent optical trap experiments have applied resisting, assisting, and sideways loads to conventional kinesin moving on microtubules at fixed [ATP]. To gain insight into intermediate motions when the motor protein takes its 8.2-nm steps, the velocity and randomness data have been analyzed by using discrete-state stochastic models with a three-dimensional "energy landscape." The bead size and tether angle play a crucial role. The analysis implies that on binding ATP the motor "crouches," the point of attachment of the tether at the necklinker junction moving downward toward the microtubule by 0.5-0.7 nm, while inching forward by only 0.1-0.2 nm, before completing the step from a transition state by a unitary "sprint" of approximately 7.8 nm. These inferences accord with high-resolution observations that exclude a previously predicted substep of 1.8-2.1 nm. Assisting and leftward loads are opposed in that the perpendicular component of the tension in the tether is enhanced by approximately 2 pN, which reduces the velocity, but sideways lurching is not supported.

Adenosine Triphosphate↗

PubMed2005

Criticality in charge-asymmetric hard-sphere ionic fluids.

Phase separation and criticality are analyzed in z:1 charge-asymmetric ionic fluids of equisized hard spheres by generalizing the Debye-Hückel approach combined with ionic association, cluster solvation by charged ions, and hard-core interactions, following lines developed by Fisher and Levin for the 1:1 case (i.e., the restricted primitive model). Explicit analytical calculations for 2:1 and 3:1 systems account for ionic association into dimers, trimers, and tetramers and subsequent multipolar cluster solvation. The reduced critical temperatures, Tc* (normalized by z), decrease with charge asymmetry, while the critical densities increase rapidly with . The results compare favorably with simulations and represent a distinct improvement over all current theories such as the mean spherical approximation, symmetric Poisson-Boltzmann theory, etc. For z not equal to 1, the interphase Galvani (or absolute electrostatic) potential difference, Deltaphi(T), between coexisting liquid and vapor phases is calculated and found to vanish as absolute value (T-Tc) beta when T-->Tc-with, since our approximations are classical, beta = (1/2). Above Tc, the compressibility maxima and so-called k-inflection loci (which aid the fast and accurate determination of the critical parameters) are found to exhibit a strong z dependence.

Journal Article↗

PubMed2005

Screening in ionic systems: simulations for the Lebowitz length.

Simulations of the Lebowitz length, xiL (T, rho), are reported for the restricted primitive model hard-core (diameter a) 1:1 electrolyte for densities rho approximately < 4rho(c) and T(c) approximately < T approximately < 40T(c). Finite-size effects are elucidated for the charge fluctuations in various subdomains that serve to evaluate xiL. On extrapolation to the bulk limit for T approximately > 10T(c) the exact low-density expansions are seen to fail badly when rho > 1/10 rho(c) (with rho(c)a3 approximately = 0.08). At higher densities xiL rises above the Debye length, xiD proportional to square root(T/rho), by 10%-30% (up to rho approximately =1.3rho(c)); the variation is portrayed fairly well by the generalized Debye-Hückel theory. On approaching criticality at fixed rho or fixed T, xiL (T, rho) remains finite with xiL(c) approximately = 0.30a approximately = 1.3xiD(c) but displays a weak entropylike singularity.

Journal Article↗

PubMed2005

How multivalency controls ionic criticality.

To understand how multivalency affects criticality in z:1 ionic fluids, we report an ion-cluster association theory embodying ionic solvation and excluded volume for equisized hard-sphere models with z=1-3. In accord with simulation but contradicting integral equation and field theories, the reduced critical temperature falls when z increases while the density rho(c) rises steeply. These trends can be explained semiquantitatively by noting that 80%-90% of the ions near T(c) are bound in neutral or charged clusters, depleting the ionic strength. For z not equal 1, predicted interphase Galvani potentials vanish at T(c).

Journal Article↗

PubMed2005

Convergence of fine-lattice discretization for near-critical fluids.

In simulating continuum model fluids that undergo phase separation and criticality, significant gains in computational efficiency may be had by confining the particles to the sites of a lattice of sufficiently fine spacing, a(0) (relative to the particle size, say a). But a cardinal question, investigated here, then arises; namely, How does the choice of the lattice discretization parameter, zeta identical with a/a(0), affect the values of interesting parameters, specifically, critical temperature and density, T(c) and rho(c)? Indeed, for small zeta ( less, similar 4-8) the underlying lattice can strongly influence the thermodynamic properties. A heuristic argument, essentially exact in d = 1 and d = 2 dimensions, indicates that, for models with hard-core potentials, both T(c)(zeta) and rho(c)(zeta) should converge to their continuum limits as 1/zeta((d)(+1)/2) for d </= 3 when zeta --> infinity; but the behavior of the error is highly erratic for d >/= 2. For smoother interaction potentials, the convergence is faster. Exact results for d = 1 models of van der Waals character confirm this; however, an optimal choice of zeta can improve the rate of convergence by a factor 1/zeta. For d >/= 2 models, the convergence of the second virial coefficients to their continuum limits likewise exhibits erratic behavior, which is seen to transfer similarly to T(c) and rho(c); but this can be used in various ways to enhance convergence and improve extrapolation to zeta = infinity as is illustrated using data for the restricted primitive model electrolyte.

Journal Article↗

PubMed2005

Scaling for interfacial tensions near critical endpoints.

Parametric scaling representations are obtained and studied for the asymptotic behavior of interfacial tensions in the full neighborhood of a fluid (or Ising-type) critical endpoint, i.e., as a function both of temperature and of density/order parameter or chemical potential/ordering field. Accurate nonclassical critical exponents and reliable estimates for the universal amplitude ratios are included naturally on the basis of the "extended de Gennes-Fisher" local-functional theory. Serious defects in previous scaling treatments are rectified and complete wetting behavior is represented; however, quantitatively small, but unphysical residual nonanalyticities on the wetting side of the critical isotherm are smoothed out "manually." Comparisons with the limited available observations are presented elsewhere but the theory invites new, searching experiments and simulations, e.g., for the vapor-liquid interfacial tension on the two sides of the critical endpoint isotherm for which an amplitude ratio -3.25+/-0.05 is predicted.

Journal Article↗

PubMed2004

Discretization dependence of criticality in model fluids: a hard-core electrolyte.

Grand-canonical simulations at various levels, zeta=5-20, of fine-lattice discretization are reported for the near-critical 1:1 hard-core electrolyte or restricted primitive model (RPM). With the aid of finite-size scaling analyses, it is shown convincingly that, contrary to recent suggestions, the universal critical behavior is independent of zeta (> or approximately 4), thus the continuum (zeta--> infinity ) RPM exhibits Ising-type (as against classical, self-avoiding walk, XY, etc.) criticality. A general consideration of lattice discretization provides effective extrapolation of the intrinsically erratic zeta dependence, yielding (T*(c),rho*(c)) approximately equal to (0.0493(3),0.075) for the zeta=infinity RPM.

Journal Article↗

PubMed2004

Ionic criticality: an exactly soluble model.

Gas-liquid criticality in ionic fluids is studied in exactly soluble spherical models that use interlaced sublattices to represent hard-core multicomponent systems. Short-range attractions in the uncharged fluid drive criticality, but charged ions do not alter the universality class. Debye screening remains exponential at criticality in fully ion-symmetric 1:1 models. However, ionic asymmetry couples charge and density fluctuations in a direct manner: The charge correlation length then diverges precisely as the density correlation length and the Stillinger-Lovett rule is violated at criticality.

Journal Article↗

PubMed2003

Asymmetric fluid criticality. II. Finite-size scaling for simulations.

The vapor-liquid critical behavior of intrinsically asymmetric fluids is studied in finite systems of linear dimensions L focusing on periodic boundary conditions, as appropriate for simulations. The recently propounded "complete" thermodynamic (L--> infinity) scaling theory incorporating pressure mixing in the scaling fields as well as corrections to scaling [Phys. Rev. E 67, 061506 (2003)] is extended to finite L, initially in a grand canonical representation. The theory allows for a Yang-Yang anomaly in which, when L--> infinity, the second temperature derivative (d2musigma/dT2) of the chemical potential along the phase boundary musigmaT diverges when T-->Tc-. The finite-size behavior of various special critical loci in the temperature-density or (T,rho) plane, in particular, the k-inflection susceptibility loci and the Q-maximal loci--derived from QL(T, L) is identical with 2L/ L where m is identical with rho- L--is carefully elucidated and shown to be of value in estimating Tc and rhoc. Concrete illustrations are presented for the hard-core square-well fluid and for the restricted primitive model electrolyte including an estimate of the correlation exponent nu that confirms Ising-type character. The treatment is extended to the canonical representation where further complications appear.

Computer Simulation↗

PubMed2003

Precise simulation of near-critical fluid coexistence.

We present a novel method to derive liquid-gas coexisting densities, rho(+/-)(T), from grand canonical simulations (without knowledge of T(c) or criticality class). The minima of Q(L) identical with (2)(L)/ (L) in an LxLxL box with m=rho- (L) are used to generate recursively an unbiased universal finite-size scaling function. Monte Carlo data for a hard-core square-well fluid and for the restricted primitive model electrolyte yield rho(+/-) to +/-1%-2% of rho(c) down to 1 part in 10(4)-10(3) of T(c) (and confirm well Ising character). Pressure mixing in the scaling fields is unequivocally revealed and indicates Yang-Yang ratios R(mu)=-0.04(4) and 0.2(6) for the two models, respectively.

Journal Article↗

PubMed2003

Asymmetric fluid criticality. I. Scaling with pressure mixing.

The thermodynamic behavior of a fluid near a vapor-liquid and, hence, asymmetric critical point is discussed within a general "complete" scaling theory incorporating pressure mixing in the nonlinear scaling fields as well as corrections to scaling. This theory allows for a Yang-Yang anomaly in which mu(")(sigma)(T), the second temperature derivative of the chemical potential along the phase boundary, diverges like the specific heat when T-->T(c); it also generates a leading singular term, /t/(2beta), in the coexistence curve diameter, where t[triple bond](T-T(c))/T(c). The behavior of various special loci, such as the critical isochore, the critical isotherm, the k-inflection loci, on which chi((k))[triple bond]chi(rho,T)/rho(k) (with chi=rho(2)k(B)TK(T)) and C((k))(V)[triple bond]C(V)(rho,T)/rho(k) are maximal at fixed T, is carefully elucidated. These results are useful for analyzing simulations and experiments, since particular, nonuniversal values of k specify loci that approach the critical density most rapidly and reflect the pressure-mixing coefficient. Concrete illustrations are presented for the hard-core square-well fluid and for the restricted primitive model electrolyte. For comparison, a discussion of the classical (or Landau) theory is presented briefly and various interesting loci are determined explicitly and illustrated quantitatively for a van der Waals fluid.

Journal Article↗

PubMed2003

A simple kinetic model describes the processivity of myosin-v.

Myosin-V is a motor protein responsible for organelle and vesicle transport in cells. Recent single-molecule experiments have shown that it is an efficient processive motor that walks along actin filaments taking steps of mean size close to 36 nm. A theoretical study of myosin-V motility is presented following an approach used successfully to analyze the dynamics of conventional kinesin but also taking some account of step-size variations. Much of the present experimental data for myosin-V can be well described by a two-state chemical kinetic model with three load-dependent rates. In addition, the analysis predicts the variation of the mean velocity and of the randomness-a quantitative measure of the stochastic deviations from uniform, constant-speed motion-with ATP concentration under both resisting and assisting loads, and indicates a substep of size d(0) approximately 13-14 nm (from the ATP-binding state) that appears to accord with independent observations.

Adenosine Diphosphate↗

PubMed2002

Universality class of criticality in the restricted primitive model electrolyte.

The 1:1 equisized hard-sphere electrolyte or restricted primitive model has been simulated via grand-canonical fine-discretization Monte Carlo. Newly devised unbiased finite-size extrapolation methods using loci in the temperature-density or (T,rho) plane of isothermal rho(2-k) vs pressure inflections, of Q identical with (2)/ maxima, and of canonical and C(V) criticality, yield estimates of (T(c),rho(c)) to +/-(0.04,3)%. Extrapolated exponents and Q ratio are (gamma,nu,Q(c)) = [1.24(3), 0.63(3); 0.624(2)], which support Ising (n = 1) behavior with (1.23(9), 0.630(3); 0.623(6)), but exclude classical, XY (n = 2), self-avoiding walk (n = 0), and n = 1 criticality with potentials varphi(r)>Phi/r(4.9) when r-->infinity.

Journal Article↗

PubMed2002

Phase transitions in 2:1 and 3:1 hard-core model electrolytes.

Critical temperatures, T(c), densities, rho(c), and coexistence curves for 2:1 and 3:1 hard-core model electrolytes have been found by fine-discretization Monte Carlo simulation. The size ratio of + and - ions strongly affects T(c) and rho(c); the trends contradict most current theories. Large multivalent ions screened by small monovalent counterions exhibit normal gas-liquid transitions of direct relevance to phase separation in charge-stabilized colloids. Conversely, extrapolation suggests the absence of such transitions for sufficiently small multivalent ions with large monovalent counterions.

Journal Article↗