Search bioRxiv⌕ Search

Biology subjects

Rollin, R.

Publications and source records attributed to Rollin, R..

3 recordsLinked to original sources

A Dual Homeostatic Regulation of Dry Mass and Volume Defines a Target Density in Proliferating Mammalian Cells

The concentration of macromolecules, especially proteins, is vital for cellular function and is influenced not only by synthesis and degradation but also by the total cell volume. While we understand various growth regulation mechanisms, the coupling of dry mass and volume in growing mammalian cells remains unclear. Here we show that two independent mechanisms acting in single cells --one regulating volume through biophysical modulation and the other controlling protein biosynthesis--work together to maintain macromolecular dry mass density and restore it following perturbations. These mechanisms ensure that proliferating cells remain within a specific range around a target density, providing density homeostasis at the population level. Although the target density appears consistent across different cell types, it is disrupted around cell division, upon perturbations of growth pathways and in senescent cells. It may represent an optimal value for cellular processes, ensuring the efficiency of essential intracellular functions.

cell biology↗

Bacterial growth under confinement requires transcriptional adaptation to resist metabolite-induced turgor pressure build-up

Bacterial proliferation often occurs in confined spaces, during biofilm formation, within host cells, or in specific niches during infection, creating mechanical constraints. We investigated how spatial confinement and growth-induced mechanical pressure affect bacterial physiology. Here, we found that, when proliferating in a confining microfluidic-based device with access to nutrients, Escherichia coli cells generate forces in the hundreds of kPa range. This pressure decouples growth and division, producing shorter bacteria with higher protein concentrations. This leads to cytoplasmic crowding, which ultimately arrests division and stalls protein synthesis. In this arrested state, the pressure produced by bacteria keeps increasing. A minimal theoretical model of bacterial growth predicts this novel regime of steady pressure increase in the absence of protein production, that we named overpressurization. In this regime, the Rcs pathway is activated and that abnormal shapes appear in rcs mutant populations only when they reach the overpressurized state. A uropathogenic strain of E. coli displayed the same confined growth phenotypes in vitro and requirement for Rcs in a mice model of urinary tract infection, suggesting that these pressurized regimes are relevant to understand the physiopathology of bacterial infections.

microbiology↗

Cell size scaling laws: a unified theory

The dimensions and compositions of cells are tightly regulated by active processes. This exquisite control is embodied in the robust scaling laws relating cell size, dry mass, and nuclear size. Despite accumulating experimental evidence, a unified theoretical framework is still lacking. Here, we show that these laws and their breakdown can be explained quantitatively by three simple, yet generic, physical constraints defining altogether the Pump and Leak model (PLM). Based on estimations, we clearly map the PLM coarse-grained parameters with the dominant cellular events they stem from. We propose that dry mass density homeostasis arises from the scaling between proteins and small osmolytes, mainly amino-acids and ions. Our theory predicts this scaling to naturally fail, both at senescence when DNA and RNAs are saturated by RNA polymerases and ribosomes respectively, and at mitotic entry due to the counterion release following histone tail modifications. We further show that nuclear scaling result from osmotic balance at the nuclear envelope (NE) and a large pool of metabolites, which dilutes chromatin counterions that do not scale during growth.

biophysics↗