Onion-like glycodendrimersomes from sequence-defined Janus glycodendrimers and influence of architecture on reactivity to a lectin

Abstract

A library of eight amphiphilic Janus glycodendrimers (GDs) with D-mannose (Man) headgroups, a known routing signal for lectinmediated transport processes, was constructed via an iterative modular methodology. Sequence-defined variations of the Janus GD modulate the surface density and sequence of Man after selfassembly into multilamellar glycodendrimersomes (GDSs). The spatial mode of Man presentation is decisive for formation of either unilamellar or onion-like GDS vesicles. Man presentation and Janus GD concentration determine GDS size and number of bilayers. Beyond vesicle architecture, Man topological display affects kinetics and plateau level of GDS aggregation by a tetravalent model lectin: the leguminous agglutinin Con A, which is structurally related to endogenous cargo transporters. The agglutination process was rapid, efficient, and readily reversible for onion-like GDSs, demonstrating their value as versatile tools to explore the nature of physiologically relevant glycan/lectin pairing.self-assembly | synthetic multilamellar vesicles | glycolipid mimics S upramolecular chemistry has enormous potential to help resolve fundamental questions in the realm of cell biology. One of the key challenges is the design of programmable models for vesicles and cells and their surfaces as a means of establishing a chemical platform that mimics natural features in size and shape, and also allows customized implementation of bioactive epitopes, in structural and topological terms. Natural complexity can conveniently be reduced to simple systems, whose degree of diversity can then be rationally reconstituted in a stepwise process. Focusing on surface properties, the recently gained access to uniform populations of stable glycodendrimersomes (GDSs) by a simple injection method using a solution of amphiphilic Janus glycodendrimers (GDs) as building blocks for self-assembly in a water-soluble aprotic solvent (1-3), has afforded a promising opportunity to realize this concept. Interestingly, the resulting GDSs, which have tunable surface features, can cover the size range of naturally occurring vesicles such as endo-and exosomes.

Why Do Membranes of Some Unhealthy Cells Adopt a Cubic Architecture?

“…In contrast to the GDSs assembled from 3-Man (Figure 2c) and 5a-Man (Figure 2d), which are vesicles with distinct membrane bilayers as reported previously, 36,38 4-Man formed assemblies with complex interior networks (Figure 2a). Some products of 4-Man self-assembly also include membrane bilayers (Figure 2b), which surround the bicontinuous cubic interior.…”

“…38 Seemingly subtle structural alterations, shown for the Janus GDs 3-Man [3EO(1,2,3)-3EOMan(4)] and 5a-Man [3EO(1,2,3,4,5,6,7)-3EOMan(8)-3EO(9)] in Figure 1, resulted in the formation of unilamellar and multilamellar GDSs. 36,38 …”

“…The diffraction patterns obtained from FFT analysis of cryo-TEM enabled modeling of the GDC (Figure 3; for comparison, the GDS models in the cases of 3-Man / 5a-Man are also presented). 38 The thickness of a Janus GD bilayer and the symmetry of the Pn 3̅ m lattice require that the GDC must be constructed from cubic membranes with tetrahedral water channels (Figure 3b). Along the [111] direction, different channels in different layers overlapped (Figure 3b), calling for further analysis of the cubic structure.…”

Self-Sorting and Coassembly of Fluorinated, Hydrogenated, and Hybrid Janus Dendrimers into Dendrimersomes

“…(3,4)PPVEG1-PE-(3,4,5)-3EO-G1-(OCH 3 ) 3 and (3,4,5)PPVEG1-PE-(3,4,5)-3EO-G1-(OCH 3 ) 3 self-assembled into unilamellar DSs with single bilayers, while (3,5)PPVEG1-PE-(3,4,5)-3EO-G1-(OCH 3 ) 3 and [(3,5)12G1+(3,5)PPVEG1]-PE-(3,4,5)-3EO-G1-(OCH 3 ) 3 formed multilamellar DSs. 12 In samples of hybrid R HF Janus dendrimer [(3,5)12G1+(3,5)PPVEG1]-PE-(3,4,5)-3EO-G1-(OCH 3 ) 3 , well-defined onion-like vesicles were observed, with numbers of bilayers from 2 to 11 (Figure 2b). The unilamellar vesicular assemblies from R H Janus dendrimers was reported before.…”

Bioactive cell-like hybrids coassembled from (glyco)dendrimersomes with bacterial membranes

“…6E). Giant GDSs (10,11,(28)(29)(30)(31) were assembled from the JGD JGD-7 (Fig. 6 F and G) using the protocol used for giant DSs and subsequently were tested for Gal-8-FITC binding.…”