title: Spatial partitioning improves the reliability of biochemical signaling.
abstract: Spatial heterogeneity is a hallmark of living systems, even at the molecular scale in individual cells. A key example is the partitioning of membrane-bound proteins via lipid domain formation or cytoskeleton-induced corralling. However, the impact of this spatial heterogeneity on biochemical signaling processes is poorly understood. Here, we demonstrate that partitioning improves the reliability of biochemical signaling. We exactly solve a stochastic model describing a ubiquitous motif in membrane signaling. The solution reveals that partitioning improves signaling reliability via two effects: it moderates the nonlinearity of the switching response, and it reduces noise in the response by suppressing correlations between molecules. An optimal partition size arises from a trade-off between minimizing the number of proteins per partition to improve signaling reliability and ensuring sufficient proteins per partition to maintain signal propagation. The predicted optimal partition size agrees quantitatively with experimentally observed systems. These results persist in spatial simulations with explicit diffusion barriers. Our findings suggest that molecular partitioning is not merely a consequence of the complexity of cellular substructures, but also plays an important functional role in cell signaling.
authors.affiliation: Foundation for Fundamental Research on Matter Institute for Atomic and Molecular Physics, 1098 XG, Amsterdam, The Netherlands.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mugler
authors.forename: Filipe
authors.initials: F
authors.lastname: Tostevin
authors.forename: Pieter Rein
authors.initials: PR
authors.lastname: ten Wolde
mesh_terms: D018957:CD59 Antigens / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D003198:Computer Simulation; D004058:Diffusion; D008565:Membrane Proteins / Q000737:chemistry*; D008956:Models, Chemical; D015233:Models, Statistical; D015203:Reproducibility of Results; D015398:Signal Transduction; D013269:Stochastic Processes; D018631:ras Proteins / Q000737:chemistry
chemical_list: D018957:CD59 Antigens; D008565:Membrane Proteins; D018631:ras Proteins