Mannose-Coated Fluorescent Lipid Particles to Decipher Glycoreceptor-Induced Phagocytosis

Session: 
PS2 Poster session 2 Even numbers
Code: 
P138
Location (hall): 
Foyer
Start/end time: 
Tuesday, July 2, 2019 - 15:45 to 17:15
Jean-Maurice
Mallet

Blaise Dumat1, Lorraine Montel2,3, Léa Pinon2,3, Pascal Matton1, Laurent Cattiaux1, Jacques Fattaccioli2,3Jean-Maurice Mallet1

1Laboratoire Des Biomolecules, Département de Chimie, Ecole Normale Superieure, Paris, France, 2PASTEUR, Département de Chimie, École Normale Supérieure, Paris, France, 3Institut Pierre-Gilles de Gennes pour la Microfluidique,, Paris, France

With the aim to address questions related to glycoreceptor- mediated phagocytosis, a number of synthetic lectin-binding ligands have been developed in the form of multivalent dendrimers or oligomers, some of them being fluorescent for targeted imaging of cell receptors. However, the development of synthetic ligands targeting glycoreceptors with high affinity is very demanding and time-consuming, hence pushing for alternative design routes. 

As compared to solid particles (e.g. silica or polystyrene beads) used for uptake studies, liquid particles such as liposomes or oil-in-water emulsion droplets have the distinct advantage to exhibit a fluid interface similar to that of cellular lipid bilayers. They can reproduce the mobility and clustering of interfacial ligands during the initial steps of a phagocytic event. Instead of focusing on the synthesis of complex multimeric glycosylated molecules, we herein propose a change of perspective by fabricating micrometric fluid particles coated with a monovalent sugar 

We report here on the development of mannose-coated fluorescent lipid microparticles to study the role of C-type lectin membrane receptor in phagocytosis.

The micrometric droplets of soybean oil in water emulsion were functionalized with a tailor-made fluorescent mannolipid. The amphiphilic ligand was built from a mannose unit, a lipid C11 spacer and a naphthalimide fluorophore. The droplets functionalization was followed by fluorescence microscopy as well as the interaction with concanavalin A which was used as a model lectin in vitro. 

In cellulo, the coated droplets were shown to be specifically internalized by macrophages in a receptor-dependent phagocytic pathway. The naked droplets on the other hand display very little internalization due to their low immunogenicity. 

This work thus brings new evidence that C-type lectin membrane receptors may act as phagocytic receptors. The droplets functionalization with the tailored amphiphilic fluorescent ligand and the droplets functionalization also provides new insights into the development of organic fluorescent particles that may prove useful for developing new targeted imaging tools.

Phagocytosis of fluorescent mannolipid coated oil microdroplets

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