Effect of Cholesterol on Biomimetic Membrane Curvature and Coronavirus Fusion Peptide Encapsulation

Abstract

Biomimetic cubic phases can be used for protein encapsulation in a variety of applications such as biosensors and drug delivery. Cubic phases with a high concentration of cholesterol and phospholipids were obtained herein. It is shown that the cubic phase structure can be maintained with a higher concentration of biomimetic membrane additives than has been reported previously. Opposing effects on the curvature of the membrane were observed upon the addition of phospholipids and cholesterol. Furthermore, the coronavirus fusion peptide significantly increased the negative curvature of the biomimetic membrane with cholesterol. We show that the viral fusion peptide can undergo structural changes leading to the formation of hydrophobic α-helices that insert into the lipid bilayer. This is of high importance, as a fusion peptide that induces increased negative curvature as shown by the formation of inverse hexagonal phases allows for greater contact area between two membranes, which is required for viral fusion to occur. The cytotoxicity assay showed that the toxicity toward HeLa cells was dramatically decreased when the cholesterol or peptide level in the nanoparticles increased. This suggests that the addition of cholesterol can improve the biocompatibility of the cubic phase nanoparticles, making them safer for use in biomedical applications. As the results, this work improves the potential for the biomedical end-use applications of the nonlamellar lipid nanoparticles and shows the need of systematic formulation studies due to the complex interplay of all components.

Coassembled Multicomponent Protein Nanoparticles Elicit Enhanced Antibacterial Activity

“…Also, the lack of acidic phospholipids in the outer membrane layer of erythrocytes probably makes them less sensitive to our protein nanoparticles. To further support these, it was recently reported that adding cholesterol to cubic-phase nanoparticles dramatically ameliorated their toxicity to HeLa cells . Notwithstanding, it is important to note that the cell culture models used in this study may not wholly mimic the in vivo toxicity characteristics.…”

“…To further support these, it was recently reported that adding cholesterol to cubic-phase nanoparticles dramatically ameliorated their toxicity to HeLa cells. 62 Notwithstanding, it is important to note that the cell culture models used in this study may not wholly mimic the in vivo toxicity characteristics. Regardless, for immediate use, these antibacterial nanoparticles could be used for the topical treatment of bacterial infections.…”

Cholesterols Induced Distinctive Entry of the Graphene Nanosheet into the Cell Membrane

“…Cholesterols, which are multifunctional lipids unique to the eukaryotic membrane, are distributed in various tissues with amounts varying from approximately 20 to 50% The rigid steroid ring structure of cholesterol restricts the motion of other membrane lipid tails, which thereby modulates biophysical properties of mammalian plasma membranes, such as membrane thickness, fluidity, , and flexibility. , Despite the role of cholesterols in biosystems having been reported by a large amount of literature studies, , much remains unknown about the exact roles of cholesterols and their molecular interactions on the membrane function. , Based on their effect on the membrane permeability and molecular transport ability, Canepa et al reported that the passive uptake of amphiphilic nanoparticles into fluid lipid membranes can be significantly hindered by cholesterols . Lorents et al.…”

DGet! An open source deuteration calculator for mass spectrometry data

“…In addition to changes in vibrational modes, deuterium possesses dramatically different nuclear properties when compared to protium, such as a reduced Larmor frequency (76.773 vs 500.130 MHz at 11.747 T), a 40 × decrease in the incoherent neutron scattering cross section [ 4 ], and a positive coherent neutron scattering length [ 5 ]. These nuclear properties, its low natural abundance and the similarity of C-H and C-D bonds make deuterated molecules invaluable as a tracers in metabolic studies and as contrast agents in neutron and nuclear magnetic resonance spectroscopic techniques [ 6 – 15 ]. Deuterated molecules can be synthesized using commercially available deuterated precursors (e.g., CD 3 I, CD 3 OD, DCO 2 D, CD 3 NH 2 , LiAlD 4 , NaBD 4 ) in standard chemistry techniques to produce site specific deuterated molecules [ 2 , 16 , 17 ].…”