A new ultradian rhythm in mammalian cell dry mass observed by holography

Abstract

We have discovered a new 4 h ultradian rhythm that occurs during the interphase of the cell cycle in a wide range of individual mammalian cells, including both primary and transformed cells. The rhythm was detected by holographic lens-free microscopy that follows the histories of the dry mass of thousands of single live cells simultaneously, each at a resolution of five minutes. It was vital that the rhythm was observed in inherently heterogeneous cell populations, thus eliminating synchronization and labeling bias. The rhythm is independent of circadian rhythm, and is temperature-compensated. We show that the amplitude of the fundamental frequency provides a way to quantify the effects of, chemical reagents on cells, thus shedding light on its mechanism. The rhythm is suppressed by proteostasis disruptors and is detected only in proliferating cells, suggesting that it represents a massive degradation and re-synthesis of protein every 4 h in growing cells.

Volume growth in animal cells is cell cycle dependent and shows additive fluctuations

“…Most recent studies on animal cell growth have considered the patterns of dry or buoyant mass ( Liu et al, 2020 ; Ghenim et al, 2021 ). Here, we complement this knowledge by providing a high-throughput dataset of volume trajectories in adhering cells, allowing us to compare the behavior of these different parameters.…”

Large cells activate global protein degradation to maintain cell size homeostasis

“…The rate of macromolecular growth depends on the interplay between the biosynthesis and degradation of proteins, lipids, polysaccharides, and other macromolecules (Alber and Suter, 2019). In an actively proliferating mammalian cell, proteins represent more than half of the cell's total dry mass (Mitchison, 1971), and are under active turnover (Ghenim et al, 2021;Liu et al, 2020). Total protein content also linearly scales with the dry mass and volume of cells at different cell cycle stages (Berenson et al, 2019;Kafri et al, 2013).…”

Volume growth in animal cells is cell cycle dependent and shows additive fluctuations

“…Most recent studies on animal cell growth have considered the patterns of dry or buoyant mass 9,35 . Here, we complement this knowledge by providing a high-throughput dataset of volume trajectories in adhering cells allowing us to compare the behavior of these different parameters.…”

“…Throughout the cell cycle, mass growth has been reported to oscillate periodically in HeLa cells 9,35 . We find that this phenomenon is not simply reflected by cell volume.…”

“…We found some oscillations in volume growth speed as a function of time from birth only in birth volume outliers, and not matching the period and amplitude of the mass oscillations reported previously. 9,35 (Figure 3 -Supplement 1). This finding suggests that dry-mass biosynthesis and volume growth, while being interrelated, can be independent in specific phases of the cell cycle.…”