Abstract
Lipid rafts are discrete, heterogeneous domains of phospholipids, sphingolipids, and sterols that are present in the cell membrane. They are responsible for conducting cell signaling and maintaining lipid-protein functionality. Redox-stress-induced modifications to any of their components can severely alter the mechanics and dynamics of the membrane causing impairment to the lipid-protein functionality. Here, we report on the effect of sphingomyelin (SM) in controlling membrane permeability and its role as a regulatory lipid in the presence of nitric oxide (NO). Force spectroscopy and atomic force microscopy imaging of raft-like phases (referring here to the coexistence of “liquid-ordered” and “liquid-disordered” phases in model bilayer membranes) prepared from lipids: 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC):SM:cholesterol (CH) (at three ratios) showed that the adhesion forces to pull the tip out of the membrane increased with increasing SM concentration, indicating decreased membrane permeability. However, in the presence of NO radical (1 and 5 μM), the adhesion forces decreased depending on SM concentration. The membrane was found to be stable at the ratio POPC:SM:CH (2:1:1) even when exposed to 1 μM NO. We believe that this is a critical ratio needed by the raft-like phases to maintain homeostasis under stress conditions. The stability could be due to an interplay existing between SM and CH. However, at 5 μM NO, membrane deteriorations were detected. For POPC:SM:CH (2:2:1) ratio, NO displayed a pro-oxidant behavior and damaged the membrane at both radical concentrations. These changes were reflected by the differences in the height profiles of the raft-like phases observed by atomic force microscopy imaging. Malondialdehyde (a peroxidation product) detection suggests that lipids may have undergone lipid nitroxidation. The changes were instantaneous and independent of radical concentration and incubation time. Our study underlines the need for identifying appropriate ratios in the lipid rafts of the cell membranes to withstand redox imbalances caused by radicals such as NO.
Highlights
Cell membrane can be understood as a specialized dynamic bilayer primarily composed of phospholipids, which can undergo various physical modulations in response to a biological process
Changes in the membrane permeability by varying SM concentration and respective action by nitric oxide (NO) were investigated by measuring the adhesive forces and break-through forces
After describing the effect of inclusion of SM into bilayers, we look into the action of NO on raft-like phases’’ (RLPs). 1 and 5 mM concentrations of NO were used because they are found in cells [37,38] at any given time and direct oxidation by NO is observed at lower concentrations
Summary
Cell membrane can be understood as a specialized dynamic bilayer primarily composed of phospholipids, which can undergo various physical modulations in response to a biological process. An exogenous or endogenous free radical attack on the phospholipids causes lipid peroxidation, a process that consists of three steps: 1) initiation, which includes formation of lipid peroxyl radicals [5]; 2) propagation of peroxyl radicals; and 3) its termination. Each of these steps can cause significant changes to the chemical structure of phospholipids, wherein membrane functionality can either be impaired or lost.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
