Physical constraints in polymer modeling of chromatin associations with the nuclear periphery at kilobase scale

Biology and Model Predictions of the Dynamics and Heterogeneity of Chromatin-Nuclear Lamina Interactions

“…We have recently assessed the extent to which basic physical properties of a polymer, such as stiffness and stretching, would influence its configurations near an impermeable (hard) surface representing a NL, fitted with an attraction potential towards the polymer ( Brunet et al, 2021 ). Chromatin is modeled as a polymer of hard beads of contour length L C 360 nm representing a ∼50 kb region to enable modeling interactions of small vLADs or euchromatic sub-LAD regions ( Madsen-Østerbye et al, 2022 ).…”

“…The polymer is configured with one or two ends anchored to the surface with increasing Euclidean distance d E between them, yielding a relaxed or stretched chain ( Figure 3A ). Further, by varying the persistence length L P , or stiffness, of the polymer, the behavior of euchromatin (low persistence length) or heterochromatin (higher persistence length) at the NL can be approximated ( Brunet et al, 2021 ).…”

“…Applying an attraction potential (ε ads ) from the surface elicits loop, train and tail polymer configurations whose position, size and frequency vary by tuning ε ads and physical parameters of the polymer (e.g., stiffness, contour length and d E ) (C) Interpretations of a chromatin polymer behavior at a NL surface, inferred from polymer configurations. Variations in ε ads from the surface leads to full adsorption, full desorption or various adsorption-desorption regimes; adapted from our own work ( Brunet et al, 2021 ).…”

“…Data from simulations indicate that in the absence of attraction potential from the NL surface, the polymer must be pinned by at least one bead to enable any interactions with the surface. Second, a flexible chain explores a greater area than a semi-flexible or rigid chain, so one may infer that a euchromatic region can explore a greater space near the NL than a more rigid heterochromatic domain ( Brunet et al, 2021 ). Third, interaction profiles of the polymer with the surface, described as trains, tails and loops ( Figure 3B ) during simulations suggest that more flexible (eu)chromatin as opposed to more rigid (hetero)chromatin can adopt more variable and dynamic configurations at the NL, reflecting biological observations ( Madsen-Østerbye et al, 2022 ).…”

“…In contrast, applying an attraction potential to the NL is essential for persistent interactions. Tuning this potential yields interaction profiles ranging from stable adsorption (strong potential) to stable desorption (weak potential), with in between, adsorption-desorption regimes yielding multiple configurations at the surface ( Brunet et al, 2021 ) ( Figure 3C ). These experiments together identify fundamental physical parameters which in combination contribute to predict chromatin behavior at the NL.…”