Membrane Engineering: Phase Separation in Polymeric Giant Vesicles

Rideau, Emeline; Wurm, Frederik R.; Landfester, Katharina

doi:10.1002/smll.201905230

Cited by 8 publications

(12 citation statements)

References 44 publications

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“…Vesicle phase separation is a useful technique to enhance protein-conjugated vesicles. Including optimization of TRAIL density for other TRAIL nanoparticle approaches could enhance TRAIL therapeutics in vivo. ,− From a biomaterials perspective, controlled spatial conjugation of proteins can apply to other types of vesicles with demonstrated phase separation, such as lipid–polymer hybrid vesicles , and polymersomes, , as well as in supported bilayer systems and nanoparticles for fundamental investigations into the effects of spatial arrangements on biological mechanisms. , Biological systems that are also known to be dependent on receptor clustering include immune signaling receptors , and receptor internalization. , Altogether, phase separated vesicles provide researchers a new tool to spatially control protein spacing for designing cell-mimetic systems and therapeutic nanoparticles.…”

mentioning

confidence: 99%

Lipid Phase Separation in Vesicles Enhances TRAIL-Mediated Cytotoxicity

Peruzzi

Sant'Anna

et al. 2022

Nano Lett.

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Ligand spatial presentation and density play important roles in signaling pathways mediated by cell receptors and are critical parameters when designing protein-conjugated therapeutic nanoparticles. Here, we harness lipid phase separation to spatially control the protein presentation on lipid vesicles. We use this system to improve the cytotoxicity of TNF-related apoptosis inducing ligand (TRAIL), a therapeutic anticancer protein. Vesicles with phase-separated TRAIL presentation induce more cell death in Jurkat cancer cells than vesicles with uniformly presented TRAIL, and cytotoxicity is dependent on TRAIL density. We assess this relationship in other cancer cell lines and demonstrate that phase-separated vesicles with TRAIL only enhance cytotoxicity through one TRAIL receptor, DR5, while another TRAIL receptor, DR4, is less sensitive to TRAIL density. This work demonstrates a rapid and accessible method to control protein conjugation and density on vesicles that can be adopted to other nanoparticle systems to improve receptor signaling by nanoparticles.

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mentioning

confidence: 99%

Lipid Phase Separation in Vesicles Enhances TRAIL-Mediated Cytotoxicity

Peruzzi

Sant'Anna

et al. 2022

Nano Lett.

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“…From a biomaterials perspective, controlled spatial conjugation of proteins can apply to other types of vesicles with demonstrated phase separation, such as lipidpolymer hybrid vesicles 23,45 and polymersomes. 46,47 as well as in supported bilayer systems for fundamental investigations into the effects of spatial arrangements on biological mechanisms. 48 As such, our work describes a technique to control ligand density that can be applied to a wide variety of nanoparticle types and biological studies.…”

Section: Discussionmentioning

confidence: 99%

Lipid phase separation in vesicles enhances TRAIL-mediated cytotoxicity

Peruzzi

Sant'Anna

et al. 2021

Preprint

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Ligand spatial presentation and density play important roles in many signaling pathways mediated by cell receptors and are critical parameters when designing protein-conjugated therapeutic nanoparticles. Currently, Janus particles are most often used to spatially control ligand conjugation, but the technological challenge of manufacturing Janus particles limits adoption for translational applications. Here, we demonstrate that lipid phase separation can be used to spatially control protein presentation onto lipid vesicles. We used this system to study the density dependence of TNF-related apoptosis inducing ligand (TRAIL), a model therapeutic protein that exhibits greater cytotoxicity to cancer cells when conjugated onto a vesicle surface than when administered as a soluble protein. Using assays for apoptosis and caspase activity, we show that phase separated TRAIL vesicles induced higher cytotoxicity to Jurkat cancer cells than uniformly-conjugated TRAIL vesicles, and enhanced cytotoxicity was dependent on the TRAIL domain density. We then assessed this relationship in other cancer cell lines and demonstrated that phase separated TRAIL vesicles only enhanced cytotoxicity through one TRAIL receptor, DR5, while another TRAIL receptor, DR4, was unaffected by the TRAIL density. These results indicate unique signaling requirements for each TRAIL receptor and how TRAIL therapy could be tailored depending on the relative levels of expression for cancer receptors of interest. Overall, this work demonstrates a readily adoptable method to control protein conjugation and density on bilayer vesicles that can be easily adopted to other therapeutic nanoparticle systems to improve receptor signaling of nanoparticles targeted to cancer and diseased cells.

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“…Giant unilamellar polymer vesicles (GUVs) are more challenging due to the composition of the membrane, where the polymers used have higher molecular weights and are therefore less dynamic. The formation of patchy polymer GUVs has been reported, by membrane phase separation upon formation [11] . However, triggered membrane manipulation and division of polymer GUVs have remained major challenges.…”

Section: Methodsmentioning

confidence: 99%

Membrane Manipulation of Giant Unilamellar Polymer Vesicles with a Temperature‐Responsive Polymer

et al. 2022

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Understanding the complex behavior and dynamics of cellular membranes is integral to gain insight into cellular division and fusion processes. Bottom-up synthetic cells are as a platform for replicating and probing cellular behavior. Giant polymer vesicles are more robust than liposomal counterparts, as well as having a broad range of chemical functionalities. However, the stability of the membrane can prohibit dynamic processes such as membrane phase separation and division. Here, we present a method for manipulating the membrane of giant polymersomes using a temperature responsive polymer. Upon elevation of temperature deformation and phase separation of the membrane was observed. Upon cooling, the membrane relaxed and became homogeneous again, with infrequent division of the synthetic cells.

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Membrane Engineering: Phase Separation in Polymeric Giant Vesicles

Cited by 8 publications

References 44 publications

Lipid Phase Separation in Vesicles Enhances TRAIL-Mediated Cytotoxicity

Lipid Phase Separation in Vesicles Enhances TRAIL-Mediated Cytotoxicity

Lipid phase separation in vesicles enhances TRAIL-mediated cytotoxicity

Membrane Manipulation of Giant Unilamellar Polymer Vesicles with a Temperature‐Responsive Polymer

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