Lipid oxidation induces structural changes in biomimetic membranes

Abstract

Oxidation can intimately influence and structurally compromise the levels of biological self-assembly embodied by intracellular and plasma membranes. Lipid peroxidation, a natural metabolic outcome of life with oxygen under light, is also a salient oxidation reaction in photomedicine treatments. However, the effect of peroxidation on the fate of lipid membranes remains elusive. Here we use a new photosensitizer that anchors and disperses in the membrane to achieve spatial control of the oxidizing species. We find, surprisingly, that the integrity of unsaturated unilamellar vesicles is preserved even for fully oxidized membranes. Membrane survival allows for the quantification of the transformations of the peroxidized bilayers, providing key physical and chemical information to understand the effect of lipid oxidation on protein insertion and on other mechanisms of cell function. We anticipate that spatially controlled oxidation will emerge as a new powerful strategy for tuning and evaluating lipid membranes in biomimetic media under oxidative stress.

Molecular simulations of the effects of phospholipid and cholesterol peroxidation on lipid membrane properties

“…The pure PlOOH membrane had the largest area per phospholipid and the lowest thickness among the investigated systems ( Figure 5). However, it was still stable, in qualitative agreement with earlier experimental results [46] and simulations [4]. Even when a larger membrane was simulated, no pore formation was observed ( Figure S6).…”

“…These results are analogous to the -floating‖ of the OOH groups observed in phospholipid hydroperoxides [5, 38,46]. However, due to the rigidity of the sterol backbone, the whole molecule was forced to reorient.…”

Bioadhesive giant vesicles for monitoring hydroperoxidation in lipid membranes

“…[7][8] While micropipette suction recently provided the first values for oxidized lipid area expansions, its implementation is not straightforward. In particular, pipettes have to be pulled and forged, coupled to a hydrostatic device before being monitored in the microscope objective vicinity through a high precision, i.e.…”

Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture

“…In order to demonstrate that the changes on lipid bilayer architecture are induced by the 1 O 2 produced by JL103, instead of by the simple insertion of this compound in the membrane, we observed that the increase of POPC area is reverted by the addition of 15 mM sodium azide (NaN 3 ), a well know singlet oxygen trap, yielding values comparable to the previous controls. The increase on the POPC area after incubation with JL103 may be explained by the change on the projected area of POPC after addition of the hydroperoxide group, –OOH, to the double bond of the unsaturated lipid (Figure 4a), leading to a higher area-per-lipid due to the migration of the -OOH group to the polar plane of the bilayer 15, 16 .…”