title: Role of spatial averaging in multicellular gradient sensing.
abstract: Gradient sensing underlies important biological processes including morphogenesis, polarization, and cell migration. The precision of gradient sensing increases with the length of a detector (a cell or group of cells) in the gradient direction, since a longer detector spans a larger range of concentration values. Intuition from studies of concentration sensing suggests that precision should also increase with detector length in the direction transverse to the gradient, since then spatial averaging should reduce the noise. However, here we show that, unlike for concentration sensing, the precision of gradient sensing decreases with transverse length for the simplest gradient sensing model, local excitation-global inhibition. The reason is that gradient sensing ultimately relies on a subtraction of measured concentration values. While spatial averaging indeed reduces the noise in these measurements, which increases precision, it also reduces the covariance between the measurements, which results in the net decrease in precision. We demonstrate how a recently introduced gradient sensing mechanism, regional excitation-global inhibition (REGI), overcomes this effect and recovers the benefit of transverse averaging. Using a REGI-based model, we compute the optimal two- and three-dimensional detector shapes, and argue that they are consistent with the shapes of naturally occurring gradient-sensing cell populations.
authors.affiliation: Department of Physics, Emory University, Atlanta, GA 30322, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Smith
authors.forename: Sean
authors.initials: S
authors.lastname: Fancher
authors.forename: Andre
authors.initials: A
authors.lastname: Levchenko
authors.forename: Ilya
authors.initials: I
authors.lastname: Nemenman
authors.forename: Andrew
authors.initials: A
authors.lastname: Mugler
mesh_terms: D002465:Cell Movement; D002633:Chemotaxis; D008954:Models, Biological; D015398:Signal Transduction