2013/02/26 by Andrew Mugler, Filipe Tostevin, Pieter Rein ten Wolde
Biochemistry, Genetics and Molecular Biology · #Advanced Fluorescence Microscopy Techniques #Gene Regulatory Network Analysis #Lipid Membrane Structure and Behavior #q-bio.MN
paper · pdf · doi:10.1073/pnas.1218301110
published as PNAS (2013) 110, 5927-5932 · 32 pages, 14 figures
arxiv created 2013/02/26 · openalex publication_date 2013/03/25 · arxiv updated 2013/11/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.