Cellular signaling networks function as generalized Wiener-Kolmogorov filters to suppress noise

Cellular signaling involves the transmission of environmental information through cascades of stochastic biochemical reactions, inevitably introducing noise that compromises signal fidelity. Each stage of the cascade often takes the form of a kinase-phosphatase push-pull network, a basic unit of signaling pathways whose malfunction is linked with a host of cancers. We show this ubiquitous enzymatic network motif effectively behaves as a Wiener-Kolmogorov (WK) optimal noise filter. Using concepts from umbral calculus, we generalize the linear WK theory, originally introduced in the context of communication and control engineering, to take nonlinear signal transduction and discrete molecule populations into account. This allows us to derive rigorous constraints for efficient noise reduction in this biochemical system. Our mathematical formalism yields bounds on filter performance in cases important to cellular function---like ultrasensitive response to stimuli. We highlight features of the system relevant for optimizing filter efficiency, encoded in a single, measurable, dimensionless parameter. Our theory, which describes noise control in a large class of signal transduction networks, is also useful both for the design of synthetic biochemical signaling pathways, and the manipulation of pathways through experimental probes like oscillatory input.Comment: 15 pages, 5 figures; to appear in Phys. Rev.

Anisotropic Hydrodynamic Mean-Field Theory for Semiflexible Polymers under Tension

We introduce an anisotropic mean-field approach for the dynamics of semiflexible polymers under intermediate tension, the force range where a chain is partially extended but not in the asymptotic regime of a nearly straight contour. The theory is designed to exactly reproduce the lowest order equilibrium averages of a stretched polymer, and treats the full complexity of the problem: the resulting dynamics include the coupled effects of long-range hydrodynamic interactions, backbone stiffness, and large-scale polymer contour fluctuations. Validated by Brownian hydrodynamics simulations and comparison to optical tweezer measurements on stretched DNA, the theory is highly accurate in the intermediate tension regime over a broad dynamical range, without the need for additional dynamic fitting parameters.Comment: 22 pages, 9 figures; revised version with additional calculations and experimental comparison; accepted for publication in Macromolecule

Inverted Berezinskii-Kosterlitz-Thouless Singularity and High-Temperature Algebraic Order in an Ising Model on a Scale-Free Hierarchical-Lattice Small-World Network

We have obtained exact results for the Ising model on a hierarchical lattice with a scale-free degree distribution, high clustering coefficient, and small-world behavior. By varying the probability p of long-range bonds, the entire spectrum from an unclustered, non-small-world network to a highly-clustered, small-world system is studied. We obtain analytical expressions for the degree distribution P(k) and clustering coefficient C for all p, as well as the average path length l for p=0 and 1. The Ising model on this network is studied through an exact renormalization-group transformation of the quenched bond probability distribution, using up to 562,500 probability bins to represent the distribution. For p < 0.494, we find power-law critical behavior of the magnetization and susceptibility, with critical exponents continuously varying with p, and exponential decay of correlations away from T_c. For p >= 0.494, where the network exhibits small-world character, the critical behavior radically changes: We find a highly unusual phase transition, namely an inverted Berezinskii-Kosterlitz-Thouless singularity, between a low-temperature phase with non-zero magnetization and finite correlation length and a high-temperature phase with zero magnetization and infinite correlation length. Approaching T_c from below, the magnetization and the susceptibility respectively exhibit the singularities of exp(-C/sqrt(T_c-T)) and exp(D/sqrt(T_c-T)), with C and D positive constants. With long-range bond strengths decaying with distance, we see a phase transition with power-law critical singularities for all p, an unusually narrow critical region and important corrections to power-law behavior that depend on the exponent characterizing the decay of long-range interactions.Comment: 22 pages, 19 figures; replaced with published versio