Kinney, NickHickman, MollyAnandakrishnan, RamuGarner, Harold R.2020-10-022020-10-022020-08-311932-6203e0238322http://hdl.handle.net/10919/100140Space-filling curves have been used for decades to study the folding principles of globular proteins, compact polymers, and chromatin. Formally, space-filling curves trace a single circuit through a set of points (x,y,z); informally, they correspond to a polymer melt. Although not quite a melt, the folding principles of Human chromatin are likened to the Hilbert curve: a type of space-filling curve. Hilbert-like curves in general make biologically compelling models of chromatin; in particular, they lack knots which facilitates chromatin folding, unfolding, and easy access to genes. Knot complexity has been intensely studied with the aid of Alexander polynomials; however, the approach does not generalize well to cases of more than one chromosome. Crossing complexity is an understudied alternative better suited for quantifying entanglement between chromosomes. Do Hilbert-like configurations limit crossing complexity between chromosomes? How does crossing complexity for Hilbert-like configurations compare to equilibrium configurations? To address these questions, we extend the Mansfield algorithm to enable sampling of Hilbert-like space filling curves on a simple cubic lattice. We use the extended algorithm to generate equilibrium, intermediate, and Hilbert-like configurational ensembles and compute crossing complexity between curves (chromosomes) in each configurational snapshot. Our main results are twofold: (a) Hilbert-like configurations limit entanglement between chromosomes and (b) Hilbert-like configurations do not limit entanglement in a model of S-phase DNA. Our second result is particularly surprising yet easily rationalized with a geometric argument. We explore ergodicity of the extended algorithm and discuss our results in the context of more sophisticated models of chromatin.application/pdfenCreative Commons Attribution 4.0 InternationalArticle - Refereedhttps://doi.org/10.1371/journal.pone.023832215832866178