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

Muhammad Waseem Ashraf,Alberto Diaspro,Aymeric Le Gratiet

doi:10.3390/polym13193422

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.

Highlights

Chromatin is a complex of DNA and proteins that exist in the nucleus of eukaryotic cells [1,2]
We adopted one label-free microscopy approach based on the angle-resolved scattering of circularly polarized light to characterize the structural organization of chromatin fiber
To investigate how the changes in chiral parameters of chromatin fiber induce changes in the circular intensity differential scattering (CIDS) signal, we computationally modeled chromatin fiber to know its organization in the cell cycle

Summary

Introduction

Chromatin is a complex of DNA and proteins that exist in the nucleus of eukaryotic cells [1,2]. We focused on the m14 element of the Mueller matrix This element is the circular dichroism (CD), in the absorption band of the sample, that is the differential extinction of right and left circularly polarized light [29]. In [46], an experimental approach was reported coupling the CIDS and the expansion microscopy to demonstrate its sensitivity to the organization of biopolymers; this study showed that by improving the distance between chiral groups, the new imaging contrast gives access to a better resolution of the chromatin-DNA organization in situ. The study [39] reported the CIDS imaging capabilities for the nuclear organization of chromatin DNA inside isolated cell nuclei; they showed the CIDS emission was able to distinguish the difference of compaction inside the nucleus induced by the chirality of the molecules; in comparison, the fluorescence emission was more of isotropic. The simulations method, the chromatin fiber model, and simulations results are presented

Computational Method

Chromatin Fiber Model

Results and Discussions

Conclusions