Many cellular behaviors of eukaryotes depend on the inherent spatial heterogeneities and subcellular architectures present in the cell, yet most computational models assume a uniform chemical environment or exclude structural detail. To address this limitation, we constructed a simplified model of the galactose switch system in haploid budding yeast ( Saccharomyces cerevisiae ) and examined how chemospatial heterogeneity and subcellular architectures influence Gal2p production and intracellular galactose concentrations. Spatially heterogeneous reactions were simulated using the reaction-diffusion master equation, while homogeneous reactions were modeled with ordinary differential equations, creating a hybrid framework. Guided by microscopy and biochemical data, we progressively incorporated key subcellular features, including interphase chromosome positioning, organization of endoplasmic reticulum (ER) subdomains, and spatial distribution of effective ribosomes actively translating galactose switch mRNAs. After 60 minutes of simulated biological time, incorporating spatial effects and architectures significantly altered model outcomes. Chromosome geometries modestly increased the probability of GAL2 initial activation without substantially affecting steady-state Gal2p abundance at the plasma membrane. ER geometry reduced the number of Gal2p transporters reaching the plasma membrane. Most notably, restricting ribosome distributions strongly suppressed Gal2p production and galactose uptake. Together, these findings highlight that spatial organization at multiple scales—from genome positioning to ER geometry to ribosome localization—critically shapes the quantitative dynamics of gene regulation and transport. Neglecting these features can mask key determinants of cellular behavior, while incorporating them yields more predictive models of eukaryotic regulation.
Wu et al. (Sun,) studied this question.