Redefining the Molecular Interplay between Dimethyl Sulfoxide, Lipid Bilayers, and Dehydration
Chris J. Malajczuk, Sławomir Stachura, James O. Hendry, Ricardo L. Mancera
Abstract
The potentially damaging action of dimethyl sulfoxide (DMSO) on phospholipid bilayers remains a matter of controversy. We have conducted a series of long-scale molecular dynamics simulations of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers at various levels of hydration in the presence of variable quantities of DMSO. These simulations provide evidence for a non-destructive dehydrating mechanism of action for DMSO on DOPC bilayers across a wide concentration range and levels of hydration. Specifically, under full- and low-hydration conditions, the bilayer underwent a minor lateral contraction, coinciding with surface dehydration in the presence of dilute DMSO solutions (XDMSO < 0.3). At higher DMSO concentrations, this bilayer structure was retained despite a progressive deterioration of the hydration structure at the interface. A similar convergence of bilayer structural properties was observed under dehydration conditions for 0.3 < XDMSO < 0.7. Destabilization occurred for dehydrated bilayers in the presence of XDMSO ≥ 0.7, suggesting the existence of a DMSO concentration and/or dehydration threshold. However, such DMSO concentrations far exceed those established as toxic to other cellular components. Our findings represent a computational model for DMSO–DOPC interactions that is consistent with a range of experimental characterizations, offering new molecular insights into the cryoprotective mechanisms of action of DMSO.