Heterogeneous Synthetic Vesicles toward Artificial Cells: Engineering Structure and Composition of Membranes for Multimodal Functionalities

Shin, Jooyong; Cole, Blair D.; Shan, Ting; Jang, Yeongseon

doi:10.1021/acs.biomac.1c01504

Cited by 26 publications

(25 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results can also be useful in designing a delivery carrier for POIs in drug delivery systems. Because our artificial system can be easily extended to the different combinations of proteins and lipids, as well as different lipid bilayer-based systems, it provides a versatile synthetic platform for systematic approaches to uncover the biological and biotechnological significance of protein lipidation at biological and artificial interfaces. , …”

Section: Discussionmentioning

confidence: 99%

Artificial Palmitoylation of Proteins Controls the Lipid Domain-Selective Anchoring on Biomembranes and the Raft-Dependent Cellular Internalization

et al. 2022

View full text Add to dashboard Cite

Protein palmitoylation, a post-translational modification, is universally observed in eukaryotic cells. The localization of palmitoylated proteins to highly dynamic, sphingolipid- and cholesterol-rich microdomains (called lipid rafts) on the plasma membrane has been shown to play an important role in signal transduction in cells. However, this complex biological system is not yet completely understood. Here, we used a combined approach where an artificial lipidated protein was applied to biomimetic model membranes and plasma membranes in cells to illuminate chemical and physiological properties of the rafts. Using cell-sized giant unilamellar vesicles, we demonstrated the selective partitioning of enhanced green fluorescent protein modified with a C-terminal palmitoyl moiety (EGFP-Pal) into the liquid-ordered phase consisting of saturated phospholipids and cholesterol. Using Jurkat T cells treated with an immunostimulant (concanavalin A), we observed the vesicular transport of EGFP-Pal. Further cellular studies with the treatment of methyl β-cyclodextrin revealed the cholesterol-dependent internalization of EGFP-Pal, which can be explained by a raft-dependent, caveolae-mediated endocytic pathway. The present synthetic approach using artificial and natural membrane systems can be further extended to explore the potential utility of artificially lipidated proteins at biological and artificial interfaces.

show abstract

Section: Discussionmentioning

confidence: 99%

Artificial Palmitoylation of Proteins Controls the Lipid Domain-Selective Anchoring on Biomembranes and the Raft-Dependent Cellular Internalization

et al. 2022

View full text Add to dashboard Cite

show abstract

“…We envision that this work is another tool that can be used to expand on vesicle technologies with multimodal functionalities. 59 Beyond mimicking the cell membrane, phase separation could also be used to engineer stimuli-responsive vesicles to enhance drug delivery. Phase separation can be induced through multiple stimuli including tension, 60 pH, 61 temperature, 62 small molecules, 63 peptides, 64 proteins, 65,66 and association with soluble oligomerizing molecules.…”

Section: Discussionmentioning

confidence: 99%

“…We envision that this work is another tool that can be used to expand on vesicle technologies with multimodal functionalities. 59…”

Section: Discussionmentioning

confidence: 99%

Enhancing functionalized liposome avidity to cells via lipid phase separation

Sant'Anna

Kamat

2022

Preprint

View full text Add to dashboard Cite

The addition of both cell-targeting moieties and polyethylene glycol (PEG) to nanoparticle (NP) drug delivery systems is a standard approach to improve the biodistribution, specificity, and uptake of therapeutic cargo. The spatial presentation of these molecules affects avidity of the NP to target cells in part through an interplay between the local ligand concentration and the steric hindrance imposed by PEG molecules. Here, we show that lipid phase separation in nanoparticles can modulate liposome avidity by changing the proximity of PEG and targeting protein molecules on a nanoparticle surface. Using lipid-anchored nickelnitrilotriacetic acid (Ni-NTA) as a model ligand, we demonstrate that the attachment of lipid anchored Ni-NTA and PEG molecules to distinct lipid domains in nanoparticles can enhance liposome binding to cancer cells by increasing ligand clustering and reducing steric hindrance. We then use this technique to enhance the binding of RGD-modified liposomes, which can bind to integrins overexpressed on many cancer cells. These results demonstrate the potential of lipid phase separation to modulate the spatial presentation of targeting and shielding molecules on nanocarriers, offering a powerful tool to enhance the efficacy of NP drug delivery systems.

show abstract

“…Electrophysiology with planar and droplet interface bilayers − and liposome-based swelling ,, have been utilized to exclusively study antibiotic permeation across membranes and membrane proteins. Giant unilamellar vesicles (GUVs) are another membrane models , that offer an optical method to investigate membrane processes like the transport of antibiotics , and AMP pore-forming or binding activity. − Mimicking bacterial membranes reconstituting LPS in in-vitro models, including GUV platforms, are crucial, nevertheless demanding to construct.…”

Section: Introductionmentioning

confidence: 99%

Bacterial Outer-Membrane-Mimicking Giant Unilamellar Vesicle Model for Detecting Antimicrobial Permeability

2023

View full text Add to dashboard Cite

The construction of bacterial outer membrane models with native lipids like lipopolysaccharide (LPS) is a barrier to understanding antimicrobial permeability at the membrane interface. Here, we engineer bacterial outer membrane (OM)mimicking giant unilamellar vesicles (GUVs) by constituting LPS under different pH conditions and assembled GUVs with controlled dimensions. We quantify the LPS reconstituted in GUV membranes and reveal their arrangement in the leaflets of the vesicles. Importantly, we demonstrate the applications of OM vesicles by exploring antimicrobial permeability activity across membranes. Model peptides, melittin and magainin-2, are examined where both peptides exhibit lower membrane activity in OM vesicles than vesicles devoid of LPS. Our findings reveal the mode of action of antimicrobial peptides in bacterial-membrane-mimicking models. Notably, the critical peptide concentration required to elicit activity on model membranes correlates with the cell inhibitory concentrations that revalidate our models closely mimic bacterial membranes. In conclusion, we provide an OM-mimicking model capable of quantifying antimicrobial permeability across membranes.

show abstract

Heterogeneous Synthetic Vesicles toward Artificial Cells: Engineering Structure and Composition of Membranes for Multimodal Functionalities

Cited by 26 publications

References 123 publications

Artificial Palmitoylation of Proteins Controls the Lipid Domain-Selective Anchoring on Biomembranes and the Raft-Dependent Cellular Internalization

Artificial Palmitoylation of Proteins Controls the Lipid Domain-Selective Anchoring on Biomembranes and the Raft-Dependent Cellular Internalization

Enhancing functionalized liposome avidity to cells via lipid phase separation

Bacterial Outer-Membrane-Mimicking Giant Unilamellar Vesicle Model for Detecting Antimicrobial Permeability

Contact Info

Product

Resources

About