# Intracellular dry mass density increases under growth-induced pressure

## TL;DR

This study shows that yeast cells in confined spaces accumulate more mass, leading to increased dry mass density and reduced nanoparticle movement.

## Contribution

The study reveals that growth-induced pressure causes intracellular macromolecule accumulation, affecting diffusivity in confined yeast cells.

## Key findings

- Dry mass density of yeast cells increases linearly with growth-induced pressure.
- Intracellular macromolecule accumulation explains the reduced diffusivity of nanoparticles in confined cells.
- Mass accumulation beyond homeostasis may drive restricted cell growth in confined environments.

## Abstract

Cells that proliferate in confined environments develop mechanical compressive stress, referred to as growth-induced pressure, which inhibits growth and division across various organisms. Recent studies have shown that in these confined spaces, the diffusivity of intracellular nanoparticles decreases. However, the physical mechanisms behind this reduction remain unclear. In this study, we use quantitative phase imaging to measure the refractive index and dry mass density of
Saccharomyces cerevisiae cells proliferating under confinement in a microfluidic bioreactor. Our results indicate that the observed decrease in diffusivity can be at least attributed to the intracellular accumulation of macromolecules. Furthermore, the linear scaling between cell content and growth-induced pressure suggests that the concentrations of macromolecules and osmolytes are maintained proportionally under such pressure in
S. cerevisiae.

Cell proliferation in confined environments leads to the buildup of mechanical pressure. Mechanical pressure has been associated with the decreased motion of intracellular nanoparticles, but the physical basis for this slowdown has not been revealed. In this study, we measure the change in dry mass density of budding yeast growing in a confining microfluidic chamber using quantitative phase imaging. The dry mass density of cells increases linearly with pressure, which can be explained by continued mass accumulation in constrained cell volume. Our results suggest that the accumulation of mass beyond cellular homeostasis may be the physical driver of the restricted growth of cells in a confined space.