title: Cooperative Clustering Digitizes Biochemical Signaling and Enhances its Fidelity.
abstract: Many membrane-bound molecules in cells form small clusters. It has been hypothesized that these clusters convert an analog extracellular signal into a digital intracellular signal and that this conversion increases signaling fidelity. However, the mechanism by which clusters digitize a signal and the subsequent effects on fidelity remain poorly understood. Here we demonstrate using a stochastic model of cooperative cluster formation that sufficient cooperation leads to digital signaling. We show that despite reducing the number of output states, which decreases fidelity, digitization also reduces noise in the system, which increases fidelity. The tradeoff between these effects leads to an optimal cluster size that agrees with experimental measurements.
authors.affiliation: Department of Physics and Astronomy, Purdue University, West Lafayette, Indiana.
authors.forename: Edward
authors.initials: E
authors.lastname: Roob
authors.affiliation: Systems Biology Doctoral Training Centre, University of Oxford, Oxford, United Kingdom; FOM Institute AMOLF, Amsterdam, the Netherlands.
authors.forename: Nicola
authors.initials: N
authors.lastname: Trendel
authors.affiliation: FOM Institute AMOLF, Amsterdam, the Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Rein Ten Wolde
authors.affiliation: Department of Physics and Astronomy, Purdue University, West Lafayette, Indiana; FOM Institute AMOLF, Amsterdam, the Netherlands. Electronic address: amugler@purdue.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mugler
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D008954:Models, Biological; D015398:Signal Transduction; D013269:Stochastic Processes