ArticlePLoS computational biology2010
Phase-locked signals elucidate circuit architecture of an oscillatory pathway.
Article in PLoS computational biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Frequency-Dependent Premature Differentiation of Pheochromocytoma Cells Exhibits Band-Pass Filter Behavior Correlation with Intracellular Enzyme Activation Kinetics.International journal of molecular sciences · 2025Article
- Modeling of Endothelial Calcium Responses within a Microfluidic Generator of Spatio-Temporal ATP and Shear Stress Signals.Micromachines · 2021Article
- A Two-Pulse Cellular Stimulation Test Elucidates Variability and Mechanisms in Signaling Pathways.Biophysical journal · 2019Article
- Synchronization of pancreatic islets by periodic or non-periodic muscarinic agonist pulse trains.PloS one · 2019Article
- A sharp-edge-based acoustofluidic chemical signal generator.Lab on a chip · 2018Article
- Capacitive coupling synchronizes autonomous microfluidic oscillators.Electrophoresis · 2018Article
- VEGFR1 promotes cell migration and proliferation through PLCγ and PI3K pathways.NPJ systems biology and applications · 2018Article
- New insights into mammalian signaling pathways using microfluidic pulsatile inputs and mathematical modeling.Integrative biology : quantitative biosciences from nano to macro · 2017Review
- Cellular Interrogation: Exploiting Cell-to-Cell Variability to Discriminate Regulatory Mechanisms in Oscillatory Signalling.PLoS computational biology · 2016Article
- Band-pass processing in a GPCR signaling pathway selects for NFAT transcription factor activation.Integrative biology : quantitative biosciences from nano to macro · 2015Article
- Measurement of the entrainment window of islets of Langerhans by microfluidic delivery of a chirped glucose waveform.Integrative biology : quantitative biosciences from nano to macro · 2015Article
- Integrated perfusion and separation systems for entrainment of insulin secretion from islets of Langerhans.Lab on a chip · 2015Article
- A G-protein subunit translocation embedded network motif underlies GPCR regulation of calcium oscillations.Biophysical journal · 2014Article
- Entrainment to periodic initiation and transition rates in a computational model for gene translation.PloS one · 2014Article
- Microfluidic interrogation and mathematical modeling of multi-regime calcium signaling dynamics.Integrative biology : quantitative biosciences from nano to macro · 2013Article
- Maintaining Stimulant Waveforms in Large Volume Microfluidic Cell Chambers.Microfluidics and nanofluidics · 2013Article
- Microfluidic oscillators with widely tunable periods.Lab on a chip · 2013Article
- Silibinin (Milk Thistle) potentiates ethanol-dependent hepatocellular carcinoma progression in male mice.Cancer letters · 2012Article
- Temporal gradients in microfluidic systems to probe cellular dynamics: a review.Analytica chimica acta · 2012Review
- Linear conversion of pressure into concentration, rapid switching of concentration, and generation of linear ramps of concentration in a microfluidic device.Biomicrofluidics · 2012Article
Corrections and comments
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Authors and funding
9 authors.
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Abstract
This paper introduces the concept of phase-locking analysis of oscillatory cellular signaling systems to elucidate biochemical circuit architecture. Phase-locking is a physical phenomenon that refers to a response mode in which system output is synchronized to a periodic stimulus; in some instances, the number of responses can be fewer than the number of inputs, indicative of skipped beats. While the observation of phase-locking alone is largely independent of detailed mechanism, we find that the properties of phase-locking are useful for discriminating circuit architectures because they reflect not only the activation but also the recovery characteristics of biochemical circuits. Here, this principle is demonstrated for analysis of a G-protein coupled receptor system, the M3 muscarinic receptor-calcium signaling pathway, using microfluidic-mediated periodic chemical stimulation of the M3 receptor with carbachol and real-time imaging of resulting calcium transients. Using this approach we uncovered the potential importance of basal IP3 production, a finding that has important implications on calcium response fidelity to periodic stimulation. Based upon our analysis, we also negated the notion that the Gq-PLC interaction is switch-like, which has a strong influence upon how extracellular signals are filtered and interpreted downstream. Phase-locking analysis is a new and useful tool for model revision and mechanism elucidation; the method complements conventional genetic and chemical tools for analysis of cellular signaling circuitry and should be broadly applicable to other oscillatory pathways.
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Registered trials
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