PLoS Computational Biology (Jan 2024)

Chromatin phase separated nanoregions explored by polymer cross-linker models and reconstructed from single particle trajectories.

  • Andrea Papale,
  • David Holcman

DOI
https://doi.org/10.1371/journal.pcbi.1011794
Journal volume & issue
Vol. 20, no. 1
p. e1011794

Abstract

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Phase separated domains (PSDs) are ubiquitous in cell biology, representing nanoregions of high molecular concentration. PSDs appear at diverse cellular domains, such as neuronal synapses but also in eukaryotic cell nucleus, limiting the access of transcription factors and thus preventing gene expression. We develop a generalized cross-linker polymer model, to study PSDs: we show that increasing the number of cross-linkers induces a polymer condensation, preventing access of diffusing molecules. To investigate how the PSDs restrict the motion of diffusing molecules, we compute the mean residence and first escaping times. Finally, we develop a method based on mean-square-displacement of single particle trajectories to reconstruct the properties of PSDs from the continuum range of anomalous exponents. We also show here that PSD generated by polymers do not induces a long-range attracting field (potential well), in contrast with nanodomains at neuronal synapses. To conclude, PSDs can result from condensed chromatin organization, where the number of cross-linkers controls molecular access.