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Cells are complex machines that can process information from their environment and adapt their behaviour to adverse conditions. In this classical description, the role of the intracellular space, and more specifically the cytoplasm, which is densely crowded, is often neglected. Yet, it is now well documented that variations in cytoplasmic density have an impact on cell signalling and cell growth. From the physical point of view, an increase in cytoplasmic density can provoke colloidal phase transitions, drastic decrease of diffusion rates of proteins and, as a result, cell signalling arrest. Remarkably, such observations were made across various species (bacteria, yeast and mammalian cells). This suggests that the crowding properties of cells and their impact on cell functions may represent a core physical feature of living cells. Yet, molecular crowding is usually not considered in the mechanistic description of signalling pathways. It is also neglected as a physical driver of evolution for cell size and growth rate. In addition, it is unknown how molecular crowding is regulated and how this regulation relates to that of cell growth and cell size control. Here, we set out to quantitatively study the physics of the cell interior and to shed light on the relationships between cell density, cell growth and cell dynamics. The key novelty of our project is to combine phase quantitative imaging with fluorescence and volume measurements to extract physical parameters of the cell interior while monitoring the cell growth rate and response to stress. This unprecedented combination of measurements will give a physical description of the impact of molecular crowding on cell dynamics and growth rate. This is the fundamental question, at the frontier of physics and biology, that we want to address. We anticipate that demonstrating the importance of molecular crowding can lead to major advances in our understanding of cell dynamics and cell growth rate.
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