α-Tocopherol (αtoc, vitamin E) is an essential nutrient sufficiently acquired through a balanced diet. This fat-soluble vitamin is most known for its antioxidative properties, however, its fundamental mechanism of action in cellular membranes remains unknown. To this end, we use time-resolved small angle neutron scattering (TR-SANS) and a contrast matching scheme to determine intervesicular exchange (k) and intrabilayer flip-flop (k) rates of αtoc in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) vesicles.
View Article and Find Full Text PDFCellular membranes are responsible for absorbing the effects of external perturbants for the cell's survival. Such perturbants include small ubiquitous molecules like -alcohols which were observed to exhibit anesthetic capabilities, with this effect tapering off at a cut-off alcohol chain length. To explain this cut-off effect and complement prior biochemical studies, we investigated a series of -alcohols (with carbon lengths 2-18) and their impact on several bilayer properties, including lipid flip-flop, intervesicular exchange, diffusion, membrane bending rigidity and more.
View Article and Find Full Text PDFPancratistatin (PST) and narciclasine (NRC) are natural therapeutic agents that exhibit specificity toward the mitochondria of cancerous cells and initiate apoptosis. Unlike traditional cancer therapeutic agents, PST and NRC are effective, targeted, and have limited adverse effects on neighboring healthy, noncancerous cells. Currently, the mechanistic pathway of action for PST and NRC remains elusive, which in part inhibits PST and NRC from becoming efficacious therapeutic alternatives.
View Article and Find Full Text PDFIn recent years, vaping has increased in both popularity and ease of access. This has led to an outbreak of a relatively new condition known as e-cigarette/vaping-associated lung injury (EVALI). This injury can be caused by physical interactions between the pulmonary surfactant (PS) in the lungs and toxins typically found in vaping solutions, such as medium chain triglycerides (MCT).
View Article and Find Full Text PDFThe function of vitamin E in biomembranes remains a prominent topic of discussion. As its limitations as an antioxidant persist and novel functions are discovered, our understanding of the role of vitamin E becomes increasingly enigmatic. As a group of lipophilic molecules (tocopherols and tocotrienols), vitamin E has been shown to influence the properties of its host membrane, and a wealth of research has connected vitamin E to polyunsaturated fatty acid (PUFA) lipids.
View Article and Find Full Text PDFPancratistatin (PST) is a natural antiviral alkaloid that has demonstrated specificity toward cancerous cells and explicitly targets the mitochondria. PST initiates apoptosis while leaving healthy, noncancerous cells unscathed. However, the manner by which PST induces apoptosis remains elusive and impedes the advancement of PST as a natural anticancer therapeutic agent.
View Article and Find Full Text PDFLipid domains in model membranes are routinely studied to provide insight into the physical interactions that drive raft formation in cellular membranes. Using small angle neutron scattering, contrast-matching techniques enable the detection of lipid domains ranging from tens to hundreds of nanometers which are not accessible to other techniques without the use of extrinsic probes. Here, we describe a probe-free experimental approach and model-free analysis to identify lipid domains in freely floating vesicles of ternary phase separating lipid mixtures.
View Article and Find Full Text PDFThe monomeric exchange kinetics of sub-micron particles provide insight into their stability and dynamism. Traditional techniques used to measure the intra- and inter-particle exchange often require monitoring the transfer of bulky and perturbing fluorescent labels. Time-resolved small angle neutron scattering (TR-SANS) overcomes these flaws by isotope labeling, allowing for the monomeric exchange rate determination of unperturbed, stress-free particles.
View Article and Find Full Text PDFThe outbreak of electronic-cigarette/vaping-associated lung injury (EVALI) has made thousands ill. This lung injury has been attributed to a physical interaction between toxicants from the vaping solution and the pulmonary surfactant. In particular, studies have implicated vitamin E acetate as a potential instigator of EVALI.
View Article and Find Full Text PDFThe antioxidant vitamin E is a commonly used vitamin supplement. Although the multi-billion dollar vitamin and nutritional supplement industry encourages the use of vitamin E, there is very little evidence supporting its actual health benefits. Moreover, vitamin E is now marketed as a lipid raft destabilizing anti-cancer agent, in addition to its antioxidant behaviour.
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