Does DMSO soften or stiffen cell membranes?
DMSO's effect on membranes depends on their composition and phase: it strongly alters cholesterol-free bilayers, barely touches cholesterol-rich ones, and makes red cells leak ATP even at low doses.
Source
Effect of DMSO on the Mechanical and Structural Properties of Model and Biological Membranes
Study at a glance
- Design
- Animal / in-vitro — In vitro biophysics: FTIR on multilamellar vesicles, flicker spectroscopy of giant vesicles and of single human red blood cells before/after DMSO, plus a luminescence ATP-release assay.
- N
- No single N; at least 100 vesicles screened per condition for morphology, several red cells per sample for flicker analysis, and ATP measured five times per DMSO concentration.
- Population
- Synthetic POPC/sphingomyelin bilayers with and without cholesterol, and red blood cells from healthy donors aged 20-30
- Outcome
- Main transition temperature, probe-based free volume, bending modulus, and extracellular ATP release
Structured fields used in claim comparison tables when every cited study has a complete layer.
What they did
The authors made model membranes from a two-lipid mix and from the same mix with a large amount of cholesterol, and exposed them to DMSO, a common cryoprotectant. They used infrared spectroscopy to track melting transitions and a buried probe molecule to gauge free volume, and filmed the thermal flickering of giant vesicles to extract bending rigidity. They also filmed the same red blood cells before and up to 90 minutes after adding 1, 5 or 10% DMSO, and measured ATP released from red cells.
What they found
In the two-lipid membrane DMSO raised the melting transition from 27°C to 33°C, reduced the free volume in the membrane core and made vesicles floppy with excess area, but had no measurable effect on bending rigidity; the cholesterol-rich membrane showed no change in transition or free volume but appeared to stiffen. In red cells, 1% DMSO raised the bending modulus by about 37%, 5% softened the membrane, and 10% had only a weak, transient effect. DMSO triggered significant ATP release from red cells at concentrations as low as 3%, plateauing around 5%.
The limits
What it doesn't show
Stable giant vesicles could not be formed above 5% DMSO, so model membranes were not tested at the 10% used for cryopreservation. The stiffening of the cholesterol-rich vesicles is described as apparent and unexplained, and the spread of values in that system was large. The mechanism of ATP release (regulated transport versus membrane damage) was not identified, and red-cell results come from a small number of young healthy donors without reported cell counts.
Key terms
- Bending modulus (κ)
- A measure of how much energy it takes to bend a membrane; higher values mean a stiffer membrane.
- Flicker (thermal fluctuation) spectroscopy
- Filming the random thermal wobbling of a vesicle or cell outline and fitting its mode spectrum to extract bending rigidity and tension.
- Liquid-ordered phase
- A cholesterol-rich fluid membrane phase with tightly packed, ordered lipid tails.
- Main phase transition
- The melting of lipid tails from an ordered gel state to a fluid state, seen as a shift in infrared CH2 stretching frequency.
- Cryoprotectant
- A substance such as DMSO added to cells to protect them from damage during freezing.
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Quiz yourself
Which membrane was most affected by DMSO in the model systems?
Common questions
Why does cholesterol make membranes resistant to DMSO?
Cholesterol-rich membranes are in a tightly packed liquid-ordered state with no phase transition in the range tested, so DMSO has little room to change packing or push the membrane across a phase boundary.
Is the ATP leakage relevant to cryopreservation?
Potentially: cells are often frozen in 10% DMSO, and if they lose ATP they may be less viable after thawing, though this study did not test viability.
How can the same molecule both stiffen and soften red cell membranes?
The effect was non-monotonic in concentration: low DMSO raised bending rigidity, while moderate DMSO lowered it, consistent with different structural effects at different doses; the mechanism was not resolved.
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