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

Abstract

Significance For over a century, it has been known that the ratio of the nuclear and cytoplasm volumes (NC ratio), rather than the separate volumes, is constant among cells of many types of organisms. Changes of the NC ratio are associated with cancerous transformations, suggesting that the ratio has physiological importance. Notably, the dominant regulatory mechanism of the NC ratio has not been identified. Here, we use physical estimates of the forces implicated in nuclear volume determination and show that they are dominated by the osmotic pressure of actively transported proteins. Inspired by this, we formulate a minimal model for the cytoplasmic and nuclear volumes that predicts the NC ratio and the factors that modulate it, in agreement with published experiments.

Force-biased nuclear import sets nuclear-cytoplasmic volumetric coupling by osmosis

“…2G and S2-B). Overall, these results indicate that in mammalian cells the nucleus-cytoplasm volumetric coupling could not be simply defined by a pure osmotic equilibrium, which would lead, instead, to a constant value of the NC ratio ( 16, 17 ).…”

“…This model, calibrated with data from refs. ( 17, 25 ), suggests that moderate tension changes may affect nuclear size through this effect (SI appendix and Fig 4A-B and S3E). Hence, we tested this hypothesis experimentally.…”

“…S3 A-B) ( 22 ). We also used a set of simple biophysical models to rationalize the results (see SI appendix) ( 16, 17 ). In the basic version of this model, NC volumes are set only by osmosis and surface tensions are negligible.…”

Bringing balance to the (osmotic) force

“…Two recent papers have addressed this question independently and come to the same conclusion in Figure 1: From [2] serendipitously complementary ways. The main common finding from both papers is that the nuclear volume does not depend on the amount of genetic material or some complex regulation mechanism, but that purely physical forces (specifically osmotic forces) are sufficient to set nuclear size and explain the N/C ratio robustness.…”

“…In the first recommended paper, Deviri and Safran [2] do a systematic analysis of the important physical forces involved and come up with bounds and estimates for their magnitudes. To understand the forces involved, we need to look a bit more closely at the nucleus which contains the genetic material in the form of chromatin (which forms chromosomes and is composed of DNA condensed with histones and other accessory proteins) within a nuclear envelope (see fig.…”