56 research outputs found
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
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