Dataset Information

Constraining Polymers into β-Turns: Miscibility and Phase Segregation Effects in Lipid Monolayers.

ABSTRACT: Abstract: Investigation of model biomembranes and their interactions with natural or synthetic macromolecules are of great interest to design membrane systems with specific properties such as drug-delivery. Here we study the behavior of amphiphilic β-turn mimetic polymer conjugates at the air⁻water interface and their interactions with lipid model membranes. For this endeavor we synthesized two different types of conjugates containing either hydrophobic polyisobutylene (PIB, Mn = 5000 g·mol-1) or helical poly(n-hexyl isocyanate) (PHIC, Mn = 4000 g·mol-1), both polymers being immiscible, whereas polyisobutylene as a hydrophobic polymer can incorporate into lipid membranes. The conjugates were investigated using Langmuir-film techniques coupled with epifluorescence microscopy and AFM (Atomic Force Microscopy), in addition to their phase behavior in mixed lipid/polymer membranes composed of DPPC (dipalmitoyl-sn-glycero-3-phosphocholine). It was found that the DPPC monolayers are strongly disturbed by the presence of the polymer conjugates and that domain formation of the polymer conjugates occurs at high surface pressures (π > 30 mN·m-1).

SUBMITTER: Deike S

PROVIDER: S-EPMC6418963 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Constraining Polymers into β-Turns: Miscibility and Phase Segregation Effects in Lipid Monolayers.

Deike Stefanie S Malke Marlen M Lechner Bob-Dan BD Binder Wolfgang H WH

Polymers 20170817 8

Abstract: Investigation of model biomembranes and their interactions with natural or synthetic macromolecules are of great interest to design membrane systems with specific properties such as drug-delivery. Here we study the behavior of amphiphilic β-turn mimetic polymer conjugates at the air⁻water interface and their interactions with lipid model membranes. For this endeavor we synthesized two different types of conjugates containing either hydrophobic polyisobutylene (PIB, M</ ...[more]

PMID: 30971043

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Project description:Phospholipid-coated targeted microbubbles are ultrasound contrast agents that can be used for molecular imaging and enhanced drug delivery. However, a better understanding is needed of their targeting capabilities and how they relate to microstructures in the microbubble coating. Here, we investigated the ligand distribution, lipid phase behavior, and their correlation in targeted microbubbles of clinically relevant sizes, coated with a ternary mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), with PEG40-stearate and DSPE-PEG2000. To investigate the effect of lipid handling prior to microbubble production in DSPC-based microbubbles, the components were either dispersed in aqueous medium (direct method) or first dissolved and mixed in an organic solvent (indirect method). To determine the lipid-phase behavior of all components, experiments were conducted on monolayers at the air/water interface. In comparison to pure DSPC and DPPC, the ternary mixtures had an additional transition plateau around 10-12 mN/m. As confirmed by infrared reflection absorption spectroscopy (IRRAS), this plateau was due to a transition in the conformation of the PEGylated components (mushroom to brush). While the condensed phase domains had a different morphology in the ternary DPPC and DSPC monolayers on the Langmuir trough, the domain morphology was similar in the coating of both ternary DPPC and DSPC microbubbles (1.5-8 μm diameter). The ternary DPPC microbubbles had a homogenous ligand distribution and significantly less liquid condensed (LC) phase area in their coating than the DSPC-based microbubbles. For ternary DSPC microbubbles, the ligand distribution and LC phase area in the coating depended on the lipid handling. The direct method resulted in a heterogeneous ligand distribution, less LC phase area than the indirect method, and the ligand colocalizing with the liquid expanded (LE) phase area. The indirect method resulted in a homogenous ligand distribution with the largest LC phase area. In conclusion, lipid handling prior to microbubble production is of importance for a ternary mixture of DSPC, PEG40-stearate, and DSPE-PEG2000.

Project description:Lipid rafts are thought to be key organizers of membrane-protein complexes in cells. Many proteins that interact with rafts have bulky polymeric components such as intrinsically disordered protein domains and polysaccharide chains. Therefore, understanding the interaction between membrane domains and membrane-bound polymers provides insights into the roles rafts play in cells. Multiple studies have demonstrated that high concentrations of membrane-bound polymeric domains create significant lateral steric pressure at membrane surfaces. Furthermore, our recent work has shown that lateral steric pressure at membrane surfaces opposes the assembly of membrane domains. Building on these findings, here we report that membrane-bound polymers are potent suppressors of membrane phase separation, which can destabilize lipid domains with substantially greater efficiency than globular domains such as membrane-bound proteins. Specifically, we created giant vesicles with a ternary lipid composition, which separated into coexisting liquid ordered and disordered phases. Lipids with saturated tails and poly(ethylene glycol) (PEG) chains conjugated to their head groups were included at increasing molar concentrations. When these lipids were sparse on the membrane surface they partitioned to the liquid ordered phase. However, as they became more concentrated, the fraction of GUVs that were phase-separated decreased dramatically, ultimately yielding a population of homogeneous membrane vesicles. Experiments and physical modeling using compositions of increasing PEG molecular weight and lipid miscibility phase transition temperature demonstrate that longer polymers are the most efficient suppressors of membrane phase separation when the energetic barrier to lipid mixing is low. In contrast, as the miscibility transition temperature increases, longer polymers are more readily driven out of domains by the increased steric pressure. Therefore, the concentration of shorter polymers required to suppress phase separation decreases relative to longer polymers. Collectively, our results demonstrate that crowded, membrane-bound polymers are highly efficient suppressors of phase separation and suggest that the ability of lipid domains to resist steric pressure depends on both their lipid composition and the size and concentration of the membrane-bound polymers they incorporate.

Dataset Information

Constraining Polymers into β-Turns: Miscibility and Phase Segregation Effects in Lipid Monolayers.

Publications

Constraining Polymers into β-Turns: Miscibility and Phase Segregation Effects in Lipid Monolayers.

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