Spatially Constrained Monte Carlo Permutation Test Reveals Diffusion Changes Near Stress Granules
- 1University of South Carolina
Abstract
Intracellular diffusion is inherently heterogeneous, yet single-particle tracking (SPT) analyses are often summarized using cell-wide average parameters that can obscure localized effects. Here, we tracked 40-nm genetically encoded multimeric (GEM) nanoparticles during stress granule (SG) formation and developed SPaCe-MC (Spatially Constrained Monte Carlo permutation test), a statistical framework that generates cytoplasm-specific null models to test whether diffusion associated with a specific cellular structure differs from that expected in the surrounding heterogeneous cytoplasm. Across three SG-inducing conditions, including oxidative stress, DDX3 inhibition, and combined treatment, bulk cytoplasmic analyses revealed distinct responses ranging from increased nanoparticle mobility to increased subdiffusive behavior. In contrast, SPaCe-MC consistently detected a local diffusion constraint in SG-associated regions relative to their treatment-matched cytoplasmic background, revealing a conserved local diffusion effect despite divergent global cytoplasmic responses. Together, our findings establish SPaCe-MC as a framework for identifying compartment-specific diffusion changes in heterogeneous cellular environments.
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BibTeX
@misc{korunova2026spatially,
title = {{Spatially Constrained Monte Carlo Permutation Test Reveals Diffusion Changes Near Stress Granules}},
author = {E. Korunova and V. Sikirzhytski and J. L. Twiss and M. Shtutman and P. Vasquez},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.17.752460},
url = {https://www.biorxiv.org/content/10.64898/2026.09.17.752460v1},
note = {Public domain},
}
RIS
TY - UNPB
TI - Spatially Constrained Monte Carlo Permutation Test Reveals Diffusion Changes Near Stress Granules
AU - E. Korunova
AU - V. Sikirzhytski
AU - J. L. Twiss
AU - M. Shtutman
AU - P. Vasquez
PY - 2026
DA - 2026/09/17
PB - bioRxiv
DO - 10.64898/2026.09.17.752460
UR - https://www.biorxiv.org/content/10.64898/2026.09.17.752460v1
AB - Intracellular diffusion is inherently heterogeneous, yet single-particle tracking (SPT) analyses are often summarized using cell-wide average parameters that can obscure localized effects. Here, we tracked 40-nm genetically encoded multimeric (GEM) nanoparticles during stress granule (SG) formation and developed SPaCe-MC (Spatially Constrained Monte Carlo permutation test), a statistical framework that generates cytoplasm-specific null models to test whether diffusion associated with a specific cellular structure differs from that expected in the surrounding heterogeneous cytoplasm. Across three SG-inducing conditions, including oxidative stress, DDX3 inhibition, and combined treatment, bulk cytoplasmic analyses revealed distinct responses ranging from increased nanoparticle mobility to increased subdiffusive behavior. In contrast, SPaCe-MC consistently detected a local diffusion constraint in SG-associated regions relative to their treatment-matched cytoplasmic background, revealing a conserved local diffusion effect despite divergent global cytoplasmic responses. Together, our findings establish SPaCe-MC as a framework for identifying compartment-specific diffusion changes in heterogeneous cellular environments.
ER -