Single-Molecule Structure and Topology of Kinetoplast DNA Networks
The Kinetoplast DNA (kDNA) is a 2D network of mutually inter-linked DNA minicircles found in Trypanosomes that heavily resembles an “Olympic gel”. Understanding the self-assembly and replication of this structure are not only major open questions in biology but can also inform the design of synthetic topological materials such as polycatenanes, dubbed as “the Holy Grail of Polymer Chemistry” by Nobel laureate Sir Fraser Stoddart.
In this talk I will present the first high-resolution, single-molecule study of kDNA network topology using AFM and steered molecular dynamics simulations. We accurately measure the spatial distribution of DNA in the network and quantify the distribution of valence of the minicircles. Additionally, we use sub-isostatic network theory to characterise the elastic Young modulus and bending stiffness of the network, and discover that they are 10^6 and 10^3 times smaller than the ones in typical 2D materials such as lipid membranes, thus rendering the kDNA the first example of a “ultra-soft” topological gel.
Our findings explain outstanding questions in the biology of kDNA and offer single-molecule insights into the properties of a unique topological material.
