Computational Modeling of Chromatin Fiber to Characterize Its Organization Using Angle-Resolved Scattering of Circularly Polarized Light

Abstract

Understanding the structural organization of chromatin is essential to comprehend the gene functions. The chromatin organization changes in the cell cycle, and it conforms to various compaction levels. We investigated a chromatin solenoid model with nucleosomes shaped as cylindrical units arranged in a helical array. The solenoid with spherical-shaped nucleosomes was also modeled. The changes in chiral structural parameters of solenoid induced different compaction levels of chromatin fiber. We calculated the angle-resolved scattering of circularly polarized light to probe the changes in the organization of chromatin fiber in response to the changes in its chiral parameters. The electromagnetic scattering calculations were performed using discrete dipole approximation (DDA). In the chromatin structure, nucleosomes have internal interactions that affect chromatin compaction. The merit of performing computations with DDA is that it takes into account the internal interactions. We demonstrated sensitivity of the scattering signal’s angular behavior to the changes in these chiral parameters: pitch, radius, the handedness of solenoid, number of solenoid turns, the orientation of solenoid, the orientation of nucleosomes, number of nucleosomes, and shape of nucleosomes. These scattering calculations can potentially benefit applying a label-free polarized-light-based approach to characterize chromatin DNA and chiral polymers at the nanoscale level.

Roadmap on Label‐Free Super‐Resolution Imaging

“…[382] Other elements of the Mueller matrix offer the very same chance of CIDS pending a model establishing the relationship between label-free and fluorescence imaging. [370,373,374,89] 12. Super-Resolved Off-Axis Holographic Multiplexing (Natan T. Shaked * )…”

“…[368] Theoretical analysis of the optical models have shown that CIDS signatures are most sensitive to the helical parameters. [364,369,370,89] Both theory and experiments lead to the observation that the differential scattering cross section is a function of higher chiral order of important biopolymers like chromatin-DNA.…”