Interaction of 3β-Amino-5-cholestene with Phospholipids in Binary and Ternary Bilayer Membranes

Lönnfors, Max; Engberg, Oskar; Peterson, Blake R.; Slotte, J. Peter

doi:10.1021/la203589u

Cited by 7 publications

(14 citation statements)

References 59 publications

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“…[64] This synthetic steroid was found to form a liquid ordered phase very similar to cholesterol with saturated lipids, suggesting that cholesterylamine could be a good substitute for cholesterol. Consistent with this interpretation, fluorescent N -alkyl-cholesterylamines bearing neutral or negatively charged head groups such as Pennsylvania Green (PG)-Glu-β-Ala-cholesterylamine ( 1 , Figure 3) are avidly taken up by living mammalian cells, associate with the cellular plasma membrane, and accumulate in transferrin-positive early/recycling endosomes (Figure 4, panels A–D).…”

Section: Cellular Uptake and Trafficking Of Cholesterol-mimetic Mementioning

confidence: 99%

Synthetic cell surface receptors for delivery of therapeutics and probes

Hymel

Peterson

2012

Advanced Drug Delivery Reviews

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Receptor-mediated endocytosis is a highly efficient mechanism for cellular uptake of membrane-impermeant ligands. Cells use this process to acquire nutrients, initiate signal transduction, promote development, regulate neurotransmission, and maintain homeostasis. Natural receptors that participate in receptor-mediated endocytosis are structurally diverse, ranging from large transmembrane proteins to small glycolipids embedded in the outer leaflet of cellular plasma membranes. Despite their vast structural differences, these receptors share common features of binding to extracellular ligands, clustering in dynamic membrane regions that pinch off to yield intracellular vesicles, and accumulation of receptor-ligand complexes in membrane-sealed endosomes. Receptors typically dissociate from ligands in endosomes and cycle back to the cell surface, whereas internalized ligands are usually delivered into lysosomes, where they are degraded, but some can escape and penetrate into the cytosol. Here, we review efforts to develop synthetic cell surface receptors, defined as nonnatural compounds, exemplified by mimics of cholesterol, that insert into plasma membranes, bind extracellular ligands including therapeutics, probes, and endogenous proteins, and engage endocytic membrane trafficking pathways. By mimicking natural mechanisms of receptor-mediated endocytosis, synthetic cell surface receptors have the potential to function as prosthetic molecules capable of seamlessly augmenting the endocytic uptake machinery of living mammalian cells.

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Section: Cellular Uptake and Trafficking Of Cholesterol-mimetic Mementioning

confidence: 99%

Synthetic cell surface receptors for delivery of therapeutics and probes

Hymel

Peterson

2012

Advanced Drug Delivery Reviews

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“…For example, insertion of cholesterol sulfate in DMPC/DHPC bicelles prevents precipitation at lower temperatures and higher lipid concentrations allowing stabilization of the aligned phase . Replacing the polar hydroxyl headgroup of Chol-OH with a primary amine in Chol-NH 2 allows for the presence of a pH value dependent positive charge in the lipid bilayer . Furthermore, cholesteryl chloroformate and Chol-NH 2 are common headgroup modified derivatives used as starting blocks for the synthesis of more complex compounds. , …”

Section: Introductionmentioning

confidence: 99%

Understanding the Enhanced Magnetic Response of Aminocholesterol Doped Lanthanide-Ion-Chelating Phospholipid Bicelles

et al. 2017

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Cholesterol (Chol-OH) and its conjugates are powerful molecules for engineering the physicochemical and magnetic properties of phospholipid bilayers in bicelles. Introduction of aminocholesterol (3β-amino-5-cholestene, Chol-NH) in bicelles composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and the thulium-ion-chelating phospholipid 1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylene triaminepentaacetate (DMPE-DTPA/Tm) results in unprecedented high magnetic alignments by selectively tuning the magnetic susceptibility Δχ of the bilayer. However, little is known on the underlying mechanisms behind the magnetic response and, more generally, on the physicochemical forces governing a Chol-NH doped DMPC bilayer. We tackled this shortcoming with a multiscale bottom-up comparative investigation of Chol-OH and Chol-NH mixed with DMPC. First, simplified monolayer models on a Langmuir trough were employed to compare the two steroid molecules at various contents in DMPC. In a second step, a molecular dynamics (MD) simulation allowed for a more representative model of the bicelle bilayer while monitoring the amphiphiles and their interactions on the molecular level. In a final step, we moved away from the models and investigated the effect of temperature on the structure and magnetic alignment of Chol-NH doped bicelles by SANS. The DMPC/steroid monolayer studies showed that Chol-OH induces a larger condensation effect than Chol-NH at steroid contents of 16 and 20 mol %. However, this tendency was inversed at steroid contents of 10, 30, and 40 mol %. Although the MD simulation with 16 mol % steroid revealed that both compounds induce a liquid-ordered state in DMPC, the bilayer containing Chol-NH was much less ordered than the analogous system containing Chol-OH. Chol-NH underwent significantly more hydrogen bonding interactions with neighboring DMPC lipids than Chol-OH. It seems that, by altering the dynamics of the hydrophilic environment of the bicelle, Chol-NH changes the crystal field and angle of the phospholipid-lanthanide DMPE-DTPA/Tm complex. These parameters largely determine the magnetic susceptibility Δχ of the complex, explaining the SANS results, which show significant differences in magnetic alignment of the steroid doped bicelles. Highly magnetically alignable DMPC/Chol-NH/DMPE-DTPA/Tm (molar ratio 16:4:5:5) bicelles were achieved up to temperatures of 35 °C before a thermoreversible rearrangement into nonalignable vesicles occurred. The results confirm the potential of Chol-NH doped bicelles to act as building blocks for the development of the magnetically responsive soft materials of tomorrow.

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“…A rational argument is that the additive effects on lipid bilayers 37,38,46,47,53 may also work on IPA bilayers by CHOL, α-T and α-TA. As shown in Fig.…”

Section: Possible Mechanism Of Additive Effectsmentioning

confidence: 99%

“…Moreover, lots of investigations 25 57 have been devoted to the effects of sterols especially CHOL , which are incorporated in lipid bilayers for modulating their characteristics, on the phase transition behavior, vesicular bilayer rigidity, and other properties by using various techniques such as DSC 25 55 57 . Among them, the well-known condensation effect of CHOL on lipid bilayers at a temperature above their main phase transition temperatures that is, lipid bilayers in the liquid-crystalline phase, L α , making the bilayer membranes more rigid was evidenced and documented 37,38,43,46,47,53 . On the other hand, the disordering effect of CHOL, which worked on lipid bilayers at a temperatures below their main phase transition temperatures that is, lipid bilayers in the gel phase, L β , making the bilayer membranes more fluidic was also evidenced and documented 37,38,46,47,53 .…”

mentioning

confidence: 99%