Abstract
Unsaturated lipid oxidation is a fundamental process involved in different aspects of cellular bioenergetics; dysregulation of lipid oxidation is often associated with cell aging and death. To study how lipid oxidation affects membrane biophysics, we used a chlorin photosensitizer to oxidize vesicles of various lipid compositions and degrees of unsaturation in a controlled manner. We observed different shape transitions that can be interpreted as an increase in the area of the targeted membrane followed by a decrease. These area modifications induced by the chemical modification of the membrane upon oxidation were followed in situ by Raman tweezers microspectroscopy. We found that the membrane area increase corresponds to the lipids’ peroxidation and is initiated by the delocalization of the targeted double bonds in the tails of the lipids. The subsequent decrease of membrane area can be explained by the formation of cleaved secondary products. As a result of these area changes, we observe vesicle permeabilization after a time lag that is characterized in relation with the level of unsaturation. The evolution of photosensitized vesicle radius was measured and yields an estimation of the mechanical changes of the membrane over oxidation time. The membrane is both weakened and permeabilized by the oxidation. Interestingly, the effect of unsaturation level on the dynamics of vesicles undergoing photooxidation is not trivial and thus carefully discussed. Our findings shed light on the fundamental dynamic mechanisms underlying the oxidation of lipid membranes and highlight the role of unsaturations on their physical and chemical properties.
Highlights
Aerobic metabolism in cells relies on the oxidation of organic compounds such as fatty acids, allowing cells to produce energy
To vary the level of membrane unsaturation we considered 1) 18:1 giant unilamellar vesicles (GUVs), made of pure monounsaturated lipid DOPC; 2) 18:2 GUVs, composed of pure polyunsaturated lipid DLPC; and 3) 18:1/18:3 GUVs, a mixture of C18:3-PC and DOPC at 50/50 molar ratio that has a mean level of unsaturation similar to DLPC
To address the role of the geometry of the unsaturation, we used 4) 18:1 transGUVs composed of DOPC-trans lipids and 5) 18:1 D6-GUVs made of DOPC-D6 lipids
Summary
Aerobic metabolism in cells relies on the oxidation of organic compounds such as fatty acids, allowing cells to produce energy. The phospholipids that constitute cell membranes are sensitive to oxidative stress, which can lead to membrane damage, aging, and potentially cell death [1,2,3]. It is essential to consider the degree of unsaturation of fatty acids to understand the mechanisms allowing lipid membranes to withstand oxidative stress. Biological membranes contain large amounts of monoand polyunsaturated fatty acids, as well as traces of transition metals necessary for oxidative reactions. As they are constantly subjected to oxidation—in particular because of the respiratory chain—cellular membranes suffer from a variety of irreversible damages. Understanding membrane behavior with respect to their lipid unsaturation degree is an important biomedical challenge
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