Self-organisation and dynamics of 2D DNA-kinetoplast

Recent years have witnessed an ever-increasing attention on the properties of topologically interlinked (catenated) ring polymers. This class of promising topologically linked materials, includes both naturally occurring biological catenated polymers and synthetically produced DNA catenanes. The kinetoplast DNA in particular, is a unique mitochondrial structure that is common to some unicellular flagellar human pathogens. Constituting a complex structure formed by thousands of interlinked DNA-mini-rings, the kinetoplast DNA is uniquely suited as a model system for the study of 2D catenated polymers. Despite recent experimental progress, our fundamental knowledge of the theoretical physics of such two-dimensional catenated ring polymers has so far attracted limited interest. Our focus here is on understanding the structural properties of the kinetoplast under confinement or flow, with the aim of improving the fundamental understanding of the physical mechanisms that determine its self-organization.

This work is computational in nature, proposing a two-level coarse-graining strategy for the DNA minicircles that constitute the building blocks of the kinetoplast. The first level involves coarse-graining from an all-atom representation to the nucleotide level ("effective monomer level"). Proceeding to a second level of coarse-graining, DNA minicircles are viewed as “penetrable rings” and all effective physical interactions are further reduced to a center-of–mass level, point-like description. By employing a proper two-level coarse graining model, thus retaining both base-resolution and coarse-grained resolution of the topologically linked DNA constituents, our primary aim is to quantify and analyze both the effects of the flow characteristics and their interplay with polymer size and architecture. The guiding hypothesis of this project is that through the variation of the geometry and topology of 2D catenated ring polymers (degree of topological linking and contour length of the DNA minicircle building blocks), and manipulation of the properties of imposed flow, we can eventually drive the manufacturing of two-dimensional polymers with desired Gaussian curvature.

Complementary to our computational approach, a collaboration with the experimental group of Prof. Alex Klotz has been established, to provide a means of validation of our models. Recent work by the external collaborator of this project, Alexander Klotz, has experimentally established some fascinating facts about the mesoscopic structure of the kinetoplast, yet very little is known from the theoretical point of view. Our work will contribute to the understanding of the physical mechanisms that determine the selforganization and the elastic properties of the kinetoplast by employing accurate modeling across the scales.