Researchers from Skoltech, the University of Potsdam, and the Massachusetts Institute of Technology have discovered a fundamental physical law that governs the seemingly chaotic motion of chromosomes inside a living cell. This discovery helps solve a long-standing biological mystery of how two-meter long DNA molecules, packed into dense chromosomes, remain mobile enough for vital processes such as turning genes on and off. The results have been published in the Physical Review Research journal and are supported by grants from the Russian Science Foundation (No. 25-13-00277) and the German Alexander von Humboldt Foundation.
A contradiction existed for a long time: On the one hand, whole-genome analysis experiments showed that a chromosome in the cell nucleus is packed not into a loose coil but into a dense “fractal globule” — a compact and virtually immobile structure. On the other hand, direct observations of living cells demonstrated that individual sections of chromosomes move actively and rapidly. Scientists could not explain how such a dense globule could be so dynamic and facilitate rapid and efficient gene regulation.
“We developed a statistical physical model that shows that the motion of chromosome sections, as long polymer chains, obeys a universal physical law independent of the minute details of their structure. The key to the solution lies in considering not the point-like, but the collective motion of entire DNA segments. It turns out that the ability of a gene on a chromosome to shift as a whole (i.e., the diffusion coefficient of its center of mass) is inversely proportional to the number of letters in its nucleotide sequence. This is a universal principle of polymer chains, valid both in thermodynamic equilibrium and under cellular activity conditions, and is fundamentally linked to Newton’s third law,” commented the lead author of the study, Kirill Polovnikov, Assistant Professor at the Skoltech Neuro Center.
By analyzing two markers on a chromosome simultaneously, the authors were able to isolate the signal corresponding specifically to the collective motion. Calculations showed that the collective dynamics of chromosomes in the cell are not as fast as they appear when observing individual points. The extracted parameter characterizing this collective mobility was 0.77, which is lower than predicted by the simplest model and corresponds to theories viewing the chromosome as a compact polymer with topological constraints — meaning DNA strands cannot freely pass through one another, tangling into a complex globule.
The scientists managed to resolve the apparent contradiction. The chromosome is indeed a tightly packed globule, but for short genomic sequences and time intervals, its segments can behave dynamically until they encounter the topological constraints of their own complex structure. The model also predicts that if thermodynamic conditions change abruptly, as happens during transitions between cell cycle phases (including before cell division), long-range correlations arise between segments in the polymer chains, decaying according to the same universal law. This effect, predicted theoretically and confirmed by computer simulation, is a marker of the system being driven out of equilibrium and further confirms the role of collective motion in chromosome dynamics.
“Now, by experimentally tracking just two reference points on a section of a chromosome (for example, a gene), we can obtain information about its collective dynamics and the complex three-dimensional structure of the gene as a whole. This not only deepens our understanding of the fundamental principles of genome organization but also reveals the universal physical laws governing the behavior of various polymer systems under conditions far from equilibrium,” added Kirill Polovnikov.
