Nucleus size and its effect on the chromatin structure in living cells

Abstract

DNA-architectural proteins play a major role in organization of chromosomal DNA in living cells by packaging it into chromatin, whose spatial conformation is determined by an intricate interplay between the DNA-binding properties of architectural proteins and physical constraints applied to the DNA by a tight nuclear space. Yet, the exact effects of the cell nucleus size on DNA-protein interactions and chromatin structure currently remain obscure. Furthermore, there is even no clear understanding of molecular mechanisms responsible for the nucleus size regulation in living cells. To find answers to these questions, we developed a general theoretical framework based on a combination of polymer field theory and transfer-matrix calculations, which showed that the nucleus size is mainly determined by the difference between the surface tensions of the nuclear envelope and the endoplasmic reticulum membrane, as well as the osmotic pressure created by cytosolic macromolecules on the cell nucleus. In addition, the model predicted the existence of a previously unknown link between the cell nucleus size and stability of nucleosomes, providing new insights into the potential role of nuclear organization in shaping the cell response to environmental cues.

Balance of osmotic pressures determines the nuclear-to-cytoplasmic volume ratio of the cell

“…In striated muscle cells, the stress generated by contraction of the sarcomeres may periodically change (e.g., in cardiomyocytes) and exceed the magnitude of the osmotic pressures in its peak; thus, including the effect of sarcomere contraction on nuclear volume requires detailed dynamic modeling that is outside of the scope of this paper. However, for other types of cells we can neglect the pressures that originate in the chromatin or cytoskeleton, which are estimated ( Table 1 ) to be about an order of magnitude smaller, at least, than the pressures of the solutes ( 71 ). It is important to note that our estimates for the osmotic pressures of the preferentially localized proteins are based on a mean-field model that neglects the fluctuations of the protein concentrations in the two compartments.…”

Mechanisms of the Keeping and Change of Forms and Sizes of the Cell Nuclei (Review)

“…Изменение осмолярности может влиять, как на размер, так и на форму ядра, но в физиологическом диапазоне эти сдвиги не влияют на изолированные ядра [79][80]. Последние исследования свидетельствуют в пользу того, что размер ядра клеток в значительной доле определяется осмотическим давлением, создаваемым цитозольными макромолекулами на ядерной мембране, и разностью поверхностных натяжений мембраны ядра и ЭПР [81], что согласуется с предыдущими экспериментальными исследованиями, показавшими, что эти макромолекулы и кариолемма играют центральную роль в регуляции размера ядра в клетках многоклеточных [82][83][84][85][86][87][88].…”