University of Cambridge > > MRC LMB Seminar Series > LMB Seminar: Cell volume and dry mass across time scales in cultured mammalian cells: from milliseconds in migrating and circulating cells to homeostasis during cycles of growth and division

LMB Seminar: Cell volume and dry mass across time scales in cultured mammalian cells: from milliseconds in migrating and circulating cells to homeostasis during cycles of growth and division

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The volume and dry mass of a cell are two global quantities which have only been recently investigated in single live cells in a quantitative manner. The volume of cells is well described by the classical Pump-Leak Model, based on the Van’t Hoff law, which means that it depends on the most abundant species in the cells – ions and metabolites. On the other hand, the cell dry mass mostly consists of proteins.

The timescale of significant volume changes (10% or more) depends 1) on water permeation through the membrane, which can be very fast (less than a second), especially if larger pores are opened; 2) on ion fluxes, which is slower (minutes) and 3) on import/synthesis of metabolites, which is even slower (tens of minutes). Depending on the context, different processes and timescales can dominate. We also observed very fast volume changes (tens of milliseconds) but the mechanism remains unexplained.

Dry mass changes display less timescales (if one excludes loosing significant fragments of the cell) and mostly correspond to protein production on the minutes to hours timescale. In proliferating cells, dry mass increases mostly steadily at the exception of a short pause during mitosis and it appears mostly independent of volume fluctuations that cells can display when change shape or under osmotic shocks.

When cells undergo cycles of growth and division, mass and volume need to grow, in average, at the same rate, to ensure density homeostasis. Several studies have shown that density is strictly controlled in cells and display very small heterogeneity in a population of growing cells. Nevertheless, there is so far no experimentally validated model explaining how mass and volume growth are coupled in cells.

I will present our work based on single live cell measures of dry mass and volume, mostly focusing on two questions: 1) how dry mass density is maintained through cycles of growth and division, and is corrected upon perturbations – a phenomenon called dry mass density homeostasis. A major finding is that cells possess two independent homeostatic mechanisms that together define a target density towards which cells slowing converge. Together, our experiments and model demonstrate that a dual passive and active coupling between dry mass and volume growth allows correction of density fluctuations and long-term maintenance of dry mass density homeostasis in a population of proliferating mammalian cells. 2) how proliferating cells maintain a stable size distribution through cycles of growth and division – a phenomenon called size homeostasis. The general question here is how growth speed is coupled with cell cycle timing, so that cells born small or big, or cells growing at different speeds, end up showing on average the same added volume, leading to a stable size distribution in the population. I will present an hypothesis and some preliminary evidence for a coupling mechanism based on the physical properties of the nuclear envelope. I will also rapidly discuss our work on shorter timescales for volume changes.

This talk is part of the MRC LMB Seminar Series series.

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