Encapsulation of hydrophobic components in dendrimersomes and decoration of their surface with proteins and nucleic acids

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

doi:10.1073/pnas.1904868116

Encapsulation of hydrophobic components in dendrimersomes and decoration of their surface with proteins and nucleic acids

Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15378-15385. doi: 10.1073/pnas.1904868116. Epub 2019 Jul 15.

Authors

Paola Torre¹, Qi Xiao^{2

3}, Irene Buzzacchera^{2

4

5}, Samuel E Sherman², Khosrow Rahimi^{4

6}, Nina Yu Kostina^{4

6}, Cesar Rodriguez-Emmenegger^{4

6}, Martin Möller^{4

6}, Christopher J Wilson⁵, Michael L Klein⁷, Matthew C Good^{8

9}, Virgil Percec¹⁰

Affiliations

¹ Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6058.
² Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323.
³ Institute of Computational Molecular Science, Temple University, Philadelphia, PA 19122.
⁴ DWI-Leibniz Institute for Interactive Materials, 52074 Aachen, Germany.
⁵ NovioSense B.V., 6534 AT Nijmegen, The Netherlands.
⁶ Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany.
⁷ Institute of Computational Molecular Science, Temple University, Philadelphia, PA 19122; [email protected] [email protected] [email protected].
⁸ Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6058; [email protected] [email protected] [email protected].
⁹ Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6321.
¹⁰ Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323; [email protected] [email protected] [email protected].

Abstract

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.

Keywords: Janus dendrimer vesicles; biological membrane mimic; folded protein; nucleic acid; onion-like vesicles.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Dendrimers / chemical synthesis
Dendrimers / chemistry*
Green Fluorescent Proteins / chemistry
Hydrophobic and Hydrophilic Interactions*
Ligands
Liposomes / chemistry
Nitrilotriacetic Acid / chemistry
Nucleic Acids / chemistry*
Proteins / chemistry*
Surface Properties

Substances

Dendrimers
Ligands
Liposomes
Nucleic Acids
Proteins
Green Fluorescent Proteins
Nitrilotriacetic Acid