Lipid unsaturation properties govern the sensitivity of membranes to photo-induced oxidative stress

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. In order to study how lipid oxidation affects membrane biophysics, we used a chlorin photosensitizer to oxidize vesicles of various lipid compositions and degree 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 (RTM). 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

Photochemically induced cyclic morphological dynamics via degradation of autonomously produced, self-assembled polymer vesicles

“…S7a. In our observations, we found that vesicles increased their diameters by up to 2.5-fold which is much larger than a reported 4% expansion range for liposomes (which did not experience a Phoenix behavior) 54 . This can be explained by the presence of monomers and hydration within the bilayers of vesicles, which act as plasticizers in the membranes and thus provide more flexibility for the expansion of the lumen of the vesicles.…”

“…3b, c, we show that both photocatalysts are indeed vulnerable to degradation when irradiated with blue light in an oxygen-rich environment, and show reductions in their absorbance peak intensities of 24 and 22% respectively. Furthermore, the hydrophilic oxidative products formed by the degradation of m-RAFT, Ru(bpy) 3 2+ and rhodamine 6 G are capable of rapidly dissolving into the water phase and thereby increase the osmotic solute concentrations 32,46,54 .…”

Photochemically Induced Cyclic Morphological Dynamics via Degradation of Autonomously Produced Self-Assembled Polymer Vesicles

“…In our observations, we found that vesicles increased their diameters by up to 2.5-fold which is much larger than a reported 4% expansion range for liposomes (which did not experience a Phoenix behavior). 50 This can be explained by the presence of monomers and hydration within the bilayers of vesicles, which act as plasticizers in the membranes and thus provide more exibility for the expansion of the lumen of the vesicles.…”

“…As predicted by the Rayleigh-Plesset equation for a "bubble", 60 when the vesicle reaches a critical expansion maximum size the membrane implodes and the inner aqueous solution leaks out to relax the expansion pressure. This relaxation, in turn, allows resealing of the membrane through the pore-line tension 50,61 around the surface defects and results in a smaller vesicle or droplet. The growth in size and implosion episodes proceed in a successive manner as photo-degradation and osmotic imbalance continue.…”

“…Furthermore, the hydrophilic oxidative products formed by the degradation of m-RAFT, Ru(bpy) 3 2+ and rhodamine 6G are capable of rapidly dissolving into the water phase and thereby increase the osmotic solute concentrations. 44,49,50 In order to induce osmotic water in ux from the surrounding bath into the polymer cores of the vesicles, some chemicals need to degrade within the polymer cores to increase its osmotic solute concentrations. In our control experiments we found that the addition of pre-degraded macro-RAFT agents into an oxygen-poor PISA specimen prior to irradiation with microscope light, resulted in gelation instead of Phoenix dynamics which support the above degradation hypothesis.…”