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

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. Within the realm of cell biology, phase-separated domains (PSDs) emerge as pervasive nanoregions characterized by high molecular concentrations. These domains manifest in diverse cellular contexts, ranging from neuronal synapses to the nucleus of eukaryotic cells, where they intricately regulate the accessibility of molecules, particularly transcription factors, thereby modulating gene expression. In this study, we present a comprehensive investigation of PSDs through the lens of a generalized cross-linker polymer model. Our model elucidates that an augmentation in the number of cross-linkers initiates polymer condensation, creating a condensed environment that impedes the diffusion of molecules. To unravel the intricate impact of PSDs on molecular motion, we calculate mean residence and first escaping times. Introducing a novel methodology based on the mean-square-displacement of single particle trajectories, we reconstruct PSD properties across a spectrum of anomalous exponents, providing nuanced insights into their dynamic behavior. In contrast to nanodomains at neuronal synapses, PSDs generated by polymers do not create a long-range attractive field, indicating a distinctive organizational principle. In conclusion, this research advances our understanding of PSDs, portraying them as outcomes of condensed chromatin organization, where the quantitative presence of cross-linkers emerges as a pivotal determinant regulating molecular access. These insights contribute to a refined comprehension of molecular dynamics, offering a foundation for further investigations into the functional implications of PSDs in cellular processes.