Encoding biological recognition in a bicomponent cell-membrane mimic

Cesar Rodriguez-Emmenegger, Qi Xiao, Nina Yu. Kostina, Samuel E. Sherman, Khosrow Rahimi, Benjamin E. Partridge, Shangda Li, Dipankar Sahoo, Aracelee M. Reveron Perez, Irene Buzzacchera, Hong Han, Meir Kerzner (+8 others)
Self-assembling dendrimers have facilitated the discovery of periodic and quasiperiodic arrays of supramolecular architectures and the diverse functions derived from them. Examples are liquid quasicrystals and their approximants plus helical columns and spheres, including some that disregard chirality. The same periodic and quasiperiodic arrays were subsequently found in block copolymers, surfactants, lipids, glycolipids, and other complex molecules. Here we report the discovery of lamellar and
more » ... hexagonal periodic arrays on the surface of vesicles generated from sequence-defined bicomponent monodisperse oligomers containing lipid and glycolipid mimics. These vesicles, known as glycodendrimersomes, act as cell-membrane mimics with hierarchical morphologies resembling bicomponent rafts. These nanosegregated morphologies diminish sugar-sugar interactions enabling stronger binding to sugar-binding proteins than densely packed arrangements of sugars. Importantly, this provides a mechanism to encode the reactivity of sugars via their interaction with sugarbinding proteins. The observed sugar phase-separated hierarchical arrays with lamellar and hexagonal morphologies that encode biological recognition are among the most complex architectures yet discovered in soft matter. The enhanced reactivity of the sugar displays likely has applications in material science and nanomedicine, with potential to evolve into related technologies. Janus glycodendrimers | lipid rafts | nanosegregation | atomic force microscopy | galectin S oft matter self-organizes into a diversity of periodic and quasiperiodic arrays, including Frank-Kasper phases such as cubic Pm 3n, known also as the A15 phase (1-4), tetragonal P4 2 / mnm known the σ-phase (5), dodecagonal liquid quasicrystals (6-8), plus helical columns (9) and spheres (10), including some that disregard chirality. The aforementioned morphologies are responsible for a variety of functions in soft matter and biology (3, 11-15). These complex architectures, which were discovered and elucidated via structural and retrostructural analysis of libraries of self-assembling dendrons and dendrimers, employed diffraction methods analogous to those used to develop the field of structural biology (16). Later these same phases were found by the same methods (17) in block copolymers (18-22), surfactants (23-26), lipids (27-33), glycolipids (34), and in other systems (35) (36) (37) (38) . Recently, amphiphilic Janus dendrimers (JDs) (39, 40), and their sugar-presenting analogs, Janus glycodendrimers (JGDs) (41), which provide synthetic alternatives to natural lipids and glycolipids that are readily functionalized, have been reported to self-assemble in either water or buffer (42) into vesicles, named dendrimersomes (DSs) and glycodendrimersomes (GDSs) (43), respectively. They can also be made into cell-like hybrids with either bacterial (44) or human cells (45) . As with cell membranes, the bilayers of these supramolecular constructs act as a barrier between the inside and outside of DSs, GDSs, and cell-like hybrids (39, 40, 43, 44) . Selective permeation can be provided, with comparable efficiency as with liposomes (13) and polymersomes (46) , when either transmembrane proteins or their mimics are incorporated into the bilayer (44). Thus, DSs and GDSs can be used as biological-membrane mimics to elucidate concepts in cell biology and glycobiology, such as compartmentalization, encapsulation and release, selective transport (39, 40, 43, 44) , as well as fusion and fission (47-49). Intriguingly, while searching for the minimum concentration of sugar from JGDs that is able to aggregate proteins, we discovered that sequence-defined monodisperse JGDs containing D-lactose (Lac) or D-mannose exhibit higher activity toward sugar-binding proteins, known as lectins, on decreasing surface density of sugar (50) (51) (52) . This inverse relationship between sugar density and aggregation of lectins is opposite to what is expected Significance The seminal fluid mosaic model of the cell membranes suggests a lipid bilayer sea, in which cholesterol, proteins, glycoconjugates, and other components are swimming. Complementing this view, a microsegregated rafts model predicts clusters of components that function as relay stations for intracellular signaling and trafficking. However, elucidating the arrangement of glycoconjugates responsible for communication and recognition between cells, and cells with proteins remains a challenge. Herein, designed dendritic macromolecules are shown to self-assemble into vesicles that function as biologicalmembrane mimics with controlled density of sugar moieties on their periphery. Surprisingly, lowering sugar density elicits higher bioactivity to sugar-binding proteins. This finding informs a design principle for active complex soft matter with potential for applications in cellular biology and nanomedicine.
doi:10.18154/rwth-2020-04202 fatcat:evatx3bxm5cg5a6cuulj6242cq