Células usam açúcares para se comunicar em nível molecular

terça-feira, março 05, 2019

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, Ishita Malhotra, Martin Möller, Christopher J. Wilson, Matthew C. Good, Mark Goulian, Tobias Baumgart, Michael L. Klein, and Virgil Percec

PNAS published ahead of print February 28, 2019 

Contributed by Michael L. Klein, January 22, 2019 (sent for review December 27, 2018; reviewed by Stephen Z. D. Cheng and Timothy J. Deming)

Models of nanosegregated bilayer structures


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 biological-membrane 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.


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 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 sugar-binding 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