title: Paracrine communication maximizes cellular response fidelity in wound signaling.
abstract: Population averaging due to paracrine communication can arbitrarily reduce cellular response variability. Yet, variability is ubiquitously observed, suggesting limits to paracrine averaging. It remains unclear whether and how biological systems may be affected by such limits of paracrine signaling. To address this question, we quantify the signal and noise of Ca(2+) and ERK spatial gradients in response to an in vitro wound within a novel microfluidics-based device. We find that while paracrine communication reduces gradient noise, it also reduces the gradient magnitude. Accordingly we predict the existence of a maximum gradient signal to noise ratio. Direct in vitro measurement of paracrine communication verifies these predictions and reveals that cells utilize optimal levels of paracrine signaling to maximize the accuracy of gradient-based positional information. Our results demonstrate the limits of population averaging and show the inherent tradeoff in utilizing paracrine communication to regulate cellular response fidelity.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, United States.
authors.forename: L Naomi
authors.initials: LN
authors.lastname: Handly
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, United States.
authors.forename: Anna
authors.initials: A
authors.lastname: Pilko
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, United States.|Section for Cell and Developmental Biology , Division of Biological Sciences, University of California, San Diego, La Jolla, United States.|San Diego Center for Systems Biology, La Jolla, United States.
authors.forename: Roy
authors.initials: R
authors.lastname: Wollman
mesh_terms: D020013:Calcium Signaling; D002460:Cell Line; D006801:Humans; D056656:Lab-On-A-Chip Devices; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D019899:Paracrine Communication; D015398:Signal Transduction; D014947:Wounds and Injuries / Q000503:physiopathology*
keywords: Optimality; computational biology; human; noise reduction; paracrine signaling; systems biology; wound response