Modeling chromatin fractal structure and dynamics: Crosslinked single chain under active forces.

Area of Science:

• Computational Biology
• Polymer Physics
• Genomics

Background:

• Interphase chromatin exhibits fractal-like folding (d_f ≈ 2.77), deviating from the ideal fractal globule model (d_f = 3).
• In vivo chromatin architecture is characterized by diverse crosslinks (e.g., cohesin, Lamin-A), which are absent in simple polymer models.
• Understanding chromatin's complex structure is crucial for deciphering genome organization and function.

Purpose of the Study:

• To develop a computational model that accurately captures chromatin's fractal packing and connectivity, including the effects of crosslinks.
• To investigate the subdiffusive behavior of chromatin under different nuclear conditions using simulations.
• To compute and analyze the topological dimension of model chromatin networks.

Main Methods:

• Utilized Monte Carlo simulations of a self-interacting random-walk model with self-avoidance and Van-der-Waals attractive interactions.
• Incorporated crosslinks into the polymer model to mimic in vivo chromatin architecture.
• Performed Langevin dynamics simulations to evaluate mean square displacement (MSD) under active and thermal conditions.

Main Results:

• The model successfully replicates chromatin's fractal packing and connectivity by tuning attractive interaction strength.
• Introducing crosslinks yields a spectral dimension (d_s = 1.2), matching the Rouse model's subdiffusive behavior (MSD ∼ t^0.4).
• The study computes the topological dimension (d_l) and confirms the inequality 1 ≤ d_s ≤ d_l ≤ d_f ≤ 3.

Conclusions:

• The developed model provides a robust framework for simulating chromatin organization, accounting for both fractal properties and crosslinking.
• The findings elucidate the physical basis for chromatin's subdiffusive dynamics and its complex topological characteristics.
• This work advances our understanding of genome folding and its implications for nuclear organization.