Rational design and engineering of polypeptide/protein vesicles for advanced biological applications

Shin, Jooyong; Jang, Yeongseon

doi:10.1039/d3tb01103h

Cited by 4 publications

(4 citation statements)

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“…In vivo , we will need to determine biodistribution and lifetime following administration by different systemic and local routes to identify the most appropriate applications. Overall, given the characteristics of protein vesicles, their applications can be further expanded into new fields, such as artificial cell platforms, biosensors, and microreactors. , …”

Section: Summary and Future Outlookmentioning

confidence: 99%

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Self-Assembled Recombinant Elastin and Globular Protein Vesicles with Tunable Properties for Diverse Applications

Gray,

Rodriguez-Otero,

Champion

2024

Acc. Chem. Res.

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Conspectus Vesicles are self-assembled structures comprised of a membrane-like exterior surrounding a hollow lumen with applications in drug delivery, artificial cells, and micro-bioreactors. Lipid or polymer vesicles are the most common and are made of lipids or polymers, respectively. They are highly useful structures for many applications but it can be challenging to decorate them with proteins or encapsulate proteins in them, owing to the use of organic solvent in their formation and the large size of proteins relative to lipid or polymer molecules. By utilization of recombinant fusion proteins to make vesicles, specific protein domains can be directly incorporated while also imparting tunability and stability. Protein vesicle assembly relies on the design and use of self-assembling amphiphilic proteins. A specific protein vesicle platform made in purely aqueous conditions of a globular, functional protein fused to a glutamate-rich leucine zipper (ZE) and a thermoresponsive elastin-like polypeptide (ELP) fused to an arginine-rich leucine zipper (ZR) is discussed here. The hydrophobic conformational change of the ELP above its transition temperature drives assembly, and strong ZE/ZR binding enables incorporation of the desired functional protein. Mixing the soluble proteins on ice induces zipper binding, and then warming above the ELP transition temperature (T t) triggers the transition to and growth of protein-rich coacervates and, finally, reorganization of proteins into vesicles. Vesicle size is tunable based on salt concentration, rate of heating, protein concentration, size of the globular protein, molar ratio of the proteins, and the ELP sequence. Increasing the salt concentration decreases vesicle size by decreasing the T t, resulting in a shorter coacervation transition stage. Likewise, directly changing the heating rate also changes this time and increasing protein concentration increases coalescence. Increasing globular protein size decreases the size of the vesicle due to steric hindrance. By changing the ELP sequence, which consists of (VPGXG) n , through the guest residue (X) or number of repeats (n), T t is changed, affecting size. Additionally, the chemical nature of X variation has endowed vesicles with stimuli responsiveness and stability at physiological conditions. Protein vesicles have been used for biocatalysis, biomacromolecular drug delivery, and vaccine applications. Photo-cross-linkable vesicles were used to deliver small molecule cargo to cancer cells in vitro and antigen to immune cells in vivo. pH-responsive vesicles effectively delivered functional protein cargo, including cytochrome C, to the cytosol of cancer cells in vitro, using hydrophobic ion pairing to improve cargo distribution in the vesicles and release. The globular protein used to make the vesicles can be varied to achieve different functions. For example, enzyme vesicles exhibit biocatalysis, and antigen vesicles induce antibody and cellular immune responses after vaccination in mice. Collectively, the development and ...

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Section: Summary and Future Outlookmentioning

confidence: 99%

“…Overall, given the characteristics of protein vesicles, their applications can be further expanded into new fields, such as artificial cell platforms, biosensors, and microreactors. 47 , 48 …”

Section: Summary and Future Outlookmentioning

confidence: 99%

Self-Assembled Recombinant Elastin and Globular Protein Vesicles with Tunable Properties for Diverse Applications

Gray,

Rodriguez-Otero,

Champion

2024

Acc. Chem. Res.

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“…Polymer vesicles possessing various functions, such as pH-, thermo-, and photoresponsiveness, are also reported. ,− Nevertheless, these often rely on poly(ethylene glycol) (PEG) as a hydrophilic group, − which has been associated with low cellular uptake efficiency and the generation of anti-PEG antibodies, − potentially causing allergic reactions. Construction of nanovesicles through peptide self-assembly has also been actively studied due to their notable properties such as high biocompatibility, biodegradability, and nonimmunogenicity. − However, peptides with high flexibility and multiple amide bonds are difficult to control in their assembly. Additionally, even if a vesicle-like nanocapsule is formed by peptide assembly, it may transform into a thermodynamically stable structure including nanofibers, nanosheets, and nanotubes. ,, …”

Section: Introductionmentioning

confidence: 99%

Vesicle-like Nanocapsules Formed by Self-Assembly of Peptides with Oligoproline and -Leucine

Okamoto,

Higuchi,

Matsubara

2024

Langmuir

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Since drug carriers are envisaged to be used in a wide variety of situations and environments, nanocarriers with diverse properties, such as biocompatibility, biodegradability, nonimmunogenicity, adequate particle size, robustness, and cell permeability, are required. Here, we report the construction of novel nanocapsules with the above-mentioned features by the selfassembly of peptides composed of oligoproline and oligoleucine (i.e., H-Pro 10 Leu 4 -NH 2 and H-Pro 10 Leu 6 -NH 2 ). The peptides selforganized via hydrogen bonds and hydrophobic interactions between oligoleucine moieties to form vesicle-like nanocapsules with cationic oligoproline exposed on the surface. The guest encapsulation experiments revealed that the nanocapsules were capable of uptake of both water-soluble and insoluble compounds. Furthermore, positively charged and/or oligoproline-based peptides are known to improve cell permeability and cellular uptake, suggesting that the peptide nanocapsules are good candidates for nanocarriers to complement liposomes and polymer micelles.

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“…Synthetic membranes primarily consist of bilayer structures derived from lipids, polymers, peptides, proteins, or a mixture of these building blocks. Each type of membrane has its own advantages and disadvantages with respect to the design of synthetic cells. − Other methods of compartmentalization, such as phase separation , and hydrogels, − have also been explored to develop different types of synthetic cells.…”

Section: Introductionmentioning

confidence: 99%

Advancing Biomimetic Functions of Synthetic Cells through Compartmentalized Cell-Free Protein Synthesis

Powers,

Jang

2023

Biomacromolecules

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Synthetic cells are artificial constructs that mimic the structures and functions of living cells. They are attractive for studying diverse biochemical processes and elucidating the origins of life. While creating a living synthetic cell remains a grand challenge, researchers have successfully synthesized hundreds of unique synthetic cell platforms. One promising approach to developing more sophisticated synthetic cells is to integrate cell-free protein synthesis (CFPS) mechanisms into vesicle platforms. This makes it possible to create synthetic cells with complex biomimetic functions such as genetic circuits, autonomous membrane modifications, sensing and communication, and artificial organelles. This Review explores recent advances in the use of CFPS to impart advanced biomimetic structures and functions to bottom-up synthetic cell platforms. We also discuss the potential applications of synthetic cells in biomedicine as well as the future directions of synthetic cell research.

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Rational design and engineering of polypeptide/protein vesicles for advanced biological applications

Abstract: Synthetic vesicles have gained considerable popularity in recent years for numerous biological and medical applications. Among the various types of synthetic vesicles, the utilization of polypeptides and/or proteins as fundamental...

Cited by 4 publications

References 102 publications

Self-Assembled Recombinant Elastin and Globular Protein Vesicles with Tunable Properties for Diverse Applications

Self-Assembled Recombinant Elastin and Globular Protein Vesicles with Tunable Properties for Diverse Applications

Vesicle-like Nanocapsules Formed by Self-Assembly of Peptides with Oligoproline and -Leucine

Advancing Biomimetic Functions of Synthetic Cells through Compartmentalized Cell-Free Protein Synthesis

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