Non-equilibrium and stochastic thermodynamics
Is the inside of a living cell a glass stirred by metabolism?
Open access · cc by · source: Europe PMC
The cell interior stiffens into a glass-like solid when its energy supply is cut, but in living cells metabolic activity keeps it fluidized near a jamming point, largely independent of the actin skeleton.
Study at a glance
- Design
- Other — Lab experiment: feedback-tracking optical-trap active microrheology on PEG-coated beads inside cultured HeLa cells, comparing untreated, actin-disrupted, cell-cycle-labelled and ATP-depleted cells.
- N
- N=21 · 21 probe measurements in untreated HeLa cells; 9 for the cytochalasin D actin-disruption comparison and 9 in ATP-depleted cells.
- Population
- HeLa cells grown as a confluent epithelial-like monolayer
- Outcome
- Frequency-dependent complex shear modulus G(ω) of the cytoplasm
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Key findings
In untreated cells the shear modulus rose with the square root of frequency, the signature predicted for dense disordered colloids near jamming rather than the pattern expected for a cytoskeletal polymer network. Disrupting actin made no significant difference, and moving from G1 to S/G2 raised the moduli only modestly (about 40% and 30%). Depleting ATP added a low-frequency elastic plateau about ten times larger than in untreated cells, meaning the cytoplasm solidified without metabolic activity.
Methodology
The authors pushed tiny non-sticky beads inside HeLa cells with an oscillating optical trap and measured how the beads moved, giving the cytoplasm's elastic and viscous response across a wide frequency range. A feedback-controlled stage kept the vigorously jiggling bead in the laser focus. They compared untreated cells with cells whose actin was disrupted by drugs, cells in different interphase stages of the cell cycle, and cells starved of ATP.
Limitations
The work uses one cancer cell line in confluent monolayers and probes only the middle of the cell, so it says little about the actin-rich cell cortex or other cell types. Sample sizes are small (21, 9 and 9 measurements, and only 3 paired before-after ATP measurements), and cells in mitosis could not be measured at all. ATP depletion with metabolic poisons may also start cell death, so the stiffening may not be caused by loss of activity alone. The link to critical jamming is an interpretation consistent with the data rather than a direct test.
How this study connects
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