Cell-like hybrids from natural and synthetic amphiphiles provide a platform to engineer functions of synthetic cells and protocells. Cell membranes and vesicles prepared from human cell membranes are relatively unstable in vitro and therefore are difficult to study. The thicknesses of biological membranes and vesicles self-assembled from amphiphilic Janus dendrimers, known as dendrimersomes, are comparable. This feature facilitated the coassembly of functional cell-like hybrid vesicles from giant dendrimersomes and bacterial membrane vesicles generated from the very stable bacterial
Encapsulation of hydrophobic components in dendrimersomes and decoration of their surface with proteins and nucleic acids
Reconstructing the functions of living cells using nonnatural components is one of the great challenges of natural sciences. Compartmentalization, encapsulation, and surface decoration of globular assemblies, known as vesicles, represent key early steps in the reconstitution of synthetic cells. Here we report that vesicles self-assembled from amphiphilic Janus dendrimers, called dendrimersomes, encapsulate high concentrations of hydrophobic components and do so more efficiently than commercially available stealth liposomes assembled from phospholipid components. Multilayer onion-like dendrimersomes demonstrate a particularly high capacity for loading low-molecular weight compounds and even folded proteins. Coassembly of amphiphilic Janus dendrimers with metal-chelating ligands conjugated to amphiphilic Janus dendrimers generates dendrimersomes that selectively display folded proteins on their periphery in an oriented manner. A modular strategy for tethering nucleic acids to the surface of dendrimersomes is also demonstrated. These findings augment the functional capabilities of dendrimersomes to serve as versatile biological membrane mimics.
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- NSF-PAR ID:
- 10138599
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 116
- Issue:
- 31
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- 15378 to 15385
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Escherichia coli cell after enzymatic degradation of its outer membrane. Human cells are fragile and require only mild centrifugation to be dismantled and subsequently reconstituted into vesicles. Here we report the coassembly of human membrane vesicles with dendrimersomes. The resulting giant hybrid vesicles containing human cell membranes, their components, and Janus dendrimers are stable for at least 1 y. To demonstrate the utility of cell-like hybrid vesicles, hybrids from dendrimersomes and bacterial membrane vesicles containing YadA, a bacterial adhesin protein, were prepared. The latter cell-like hybrids were recognized by human cells, allowing for adhesion and entry of the hybrid bacterial vesicles into human cells in vitro. -
null (Ed.)The vital functions of cell membranes require their ability to quickly change shape to perform complex tasks such as motion, division, endocytosis, and apoptosis. Membrane curvature in cells is modulated by very complex processes such as changes in lipid composition, the oligomerization of curvature-scaffolding proteins, and the reversible insertion of protein regions that act like wedges in the membrane. But, could much simpler mechanisms support membrane shape transformation? In this work, we demonstrate how the change of amphiphile topology in the bilayer can drive shape transformations of cell membrane models. To tackle this, we have designed and synthesized new types of amphiphiles—Janus dendrimers—that self-assemble into uni-, multilamellar, or smectic-ordered vesicles, named dendrimersomes. We synthesized Janus dendrimers containing a photo-labile bond that upon UV-Vis irradiation cleavage lose a part of the hydrophilic dendron. This leads to a change from a cylindrically to a wedge-shaped amphiphile. The high mobility of these dendrimers allows for the concentration of the wedge-shaped amphiphiles and the generation of transmembrane asymmetries. The concentration of the wedges and their rate of segregation allowed control of the budding and generation of structures such as tubules and high genus vesicles.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1073/pnas.1904868116
