The correlation between cell and nucleus size is explained by an eukaryotic cell growth model

Abstract

In eukaryotes, the cell volume is observed to be strongly correlated with the nuclear volume. The slope of this correlation depends on the cell type, growth condition, and the physical environment of the cell. We develop a computational model of cell growth and proteome increase, incorporating the kinetics of amino acid import, protein/ribosome synthesis and degradation, and active transport of proteins between the cytoplasm and the nucleoplasm. We also include a simple model of ribosome biogenesis and assembly. Results show that the cell volume is tightly correlated with the nuclear volume, and the cytoplasm-nucleoplasm transport rates strongly influence the cell growth rate as well as the cell/nucleus volume ratio (C/N ratio). Ribosome assembly and the ratio of ribosomal proteins to mature ribosomes also influence the cell volume and the cell growth rate. We find that in order to regulate the cell growth rate and the cell/nucleus volume ratio, the cell must optimally control groups of kinetic and transport parameters together, which could explain the quantitative roles of canonical growth pathways. Finally, although not explicitly demonstrated in this work, we point out that it is possible to construct a detailed proteome distribution using our model and RNAseq data, provided that a quantitative cell division mechanism is known.

Cell size scaling laws: a unified theory

“…These conclusions may appear surprising due to the broadly reported linear scaling between volume (metabolites) and dry mass (proteins), hence enforcing a constant dry mass density ρ during growth. Many theoretical papers have assumed a priori a linear phenomenological relation between volume and protein number in order to study cell size [30],[31],[32]. Our results instead emphasize that the proportionality is indirect, only arising from the scaling between amino-acid and protein numbers.…”

“…The fact that the NC ratio remains almost constant during growth ([47], [48]) suggest that cells are closer to the NC 1 regime, and point at the crucial role of metabolites in setting the NC ratio (Fig.4 and S1.B). Importantly, these conclusions are overlooked in a large part of the existing literature ([31],[32],[41]) which often assumes that metabolites do not play any role on the NC ratio due to their permeability at the NE. We end this qualitative discussion by predicting the effect of a variation of the parameters z p , z a and α 0 that were so far assumed to be fixed.…”

“…4 and S1.B). Importantly, these conclusions are overlooked in a large part of the existing literature ( [31], [32], [41]) which often assumes that metabolites do not play any role on the NC ratio due to their permeability at the NE. We end this qualitative discussion by predicting the effect of a variation of the parameters z p , z a and α 0 that were so far assumed to be fixed.…”

Spatiotemporal expression of HMGB2 regulates cell proliferation and hepatocyte size during liver regeneration

“…In the present study, the hypertrophic hepatocytes contained significantly enlarged nuclei in HMGB2-KO livers compared to WT-littermates. This finding could be explained by the nucleoskeletal theory, where the amount of DNA influences nuclear volume as well as affecting cell size 37 , 38 . Nuclear size is proportional to the amount of DNA, and it has a pivotal role in gene expression and transcription 39 .…”

Tsc1 Haploinsufficiency Leads to Pax2 Dysregulation in the Developing Murine Cerebellum

“…The number and area of Pax2 + positive cells were automatically counted with Fiji ImageJ (Schindelin et al, 2012), using custom-written macros. 5 Given the positive correlation between nuclear and cell body size, we used the area of Pax2 + staining as a proxy for cell area (Wu et al, 2022). To calculate the distance between Pax2 + particles, we used the ND ImageJ plugin (Haeri and Haeri, 2015).…”