2019, Ludwig, Anna-Kristin, Michalak, Malwina, Xiao, Qi, Gilles, Ulrich, Medrano, Francisco J., Ma, Hanyue, FitzGerald, Forrest G., Hasley, William D., Melendez-Davila, Adriel, Liu, Matthew, Rahimi, Khosrow, Kostina, Nina Yu, Rodriguez-Emmenegger, Cesar, Möller, Martin, Lindner, Ingo, Kaltner, Herbert, Cudic, Mare, Reusch, Dietmar, Kopitz, Jürgen, Romero, Antonio, Oscarson, Stefan, Klein, Michael L., Gabius, Hans-Joachim, Percec, Virgil

Glycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of complexes of distinct signal-triggering topology on biomembranes. Faced with the challenge to understand why evolution has led to three particular modes of modular architecture for adhesion/growth-regulatory galectins in vertebrates, here we introduce protein engineering to enable design switches. The impact of changes is measured in assays on cell growth and on bridging fully synthetic nanovesicles (glycodendrimersomes) with a chemically programmable surface. Using the example of homodimeric galectin-1 and monomeric galectin-3, the mutual design conversion caused qualitative differences, i.e., from bridging effector to antagonist/from antagonist to growth inhibitor and vice versa. In addition to attaining proof-of-principle evidence for the hypothesis that chimera-type galectin-3 design makes functional antagonism possible, we underscore the value of versatile surface programming with a derivative of the pan-galectin ligand lactose. Aggregation assays with N,N′-diacetyllactosamine establishing a parasite-like surface signature revealed marked selectivity among the family of galectins and bridging potency of homodimers. These findings provide fundamental insights into design-functionality relationships of galectins. Moreover, our strategy generates the tools to identify biofunctional lattice formation on biomembranes and galectin-reagents with therapeutic potential.

2019, Torre, Paola, Xiao, Qi, Buzzacchera, Irene, Sherman, Samuel E., Rahimi, Khosrow, Kostina, Nina Yu., Rodriguez-Emmenegger, Cesar, Möller, Martin, Wilson, Christopher J., Klein, Michael L., Good, Matthew C., Percec, Virgil

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.