Redefining the Molecular Interplay between Dimethyl Sulfoxide, Lipid Bilayers, and Dehydration.

Area of Science:

• Biophysics
• Computational Chemistry
• Materials Science

Background:

• The interaction of dimethyl sulfoxide (DMSO) with phospholipid bilayers is controversial, with potential for membrane damage.
• Understanding DMSO's mechanism is crucial for its applications, particularly in cryoprotection.

Purpose of the Study:

• To investigate the molecular mechanisms of DMSO interaction with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers.
• To determine if DMSO causes destructive damage to phospholipid bilayers across various hydration levels and concentrations.
• To provide a computational model for DMSO-DOPC interactions relevant to cryoprotective effects.

Main Methods:

• Long-scale molecular dynamics simulations.
• Simulations were conducted on DOPC bilayers at varying hydration levels and DMSO concentrations (X_DMSO).

Main Results:

• DMSO acts via a non-destructive dehydrating mechanism on DOPC bilayers across a wide range of concentrations and hydration.
• Minor lateral contraction and surface dehydration observed at dilute DMSO concentrations (X_DMSO < 0.3).
• Bilayer structure is maintained even with deteriorating interfacial hydration at higher concentrations (0.3 < X_DMSO < 0.7).
• Destabilization occurs only at very high dehydrated concentrations (X_DMSO ≥ 0.7), exceeding known toxic levels.

Conclusions:

• DMSO's primary action on DOPC bilayers is dehydration, not direct structural destruction.
• A concentration and/or dehydration threshold exists for bilayer destabilization, occurring at concentrations unlikely in biological cryoprotection.
• Findings support DMSO's role as a cryoprotectant by providing a molecular model consistent with experimental data.