Tailoring Lipoplex Composition to the Lipid Composition of Plasma Membrane: A Trojan Horse for Cell Entry?

The first interaction between lipoplexes and cells is charge-mediated and not specific. Endocytosis is considered to be the main pathway for lipoplex entry. Upon interaction between lipoplexes and the plasma membrane, intermixing between lipoplex and membrane lipids is necessary for efficient endocy...

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Bibliographic Details
Published in:Langmuir 2010-09, Vol.26 (17), p.13867-13873
Main Authors: Marchini, Cristina, Pozzi, Daniela, Montani, Maura, Alfonsi, Cinzia, Amici, Augusto, Amenitsch, Heinz, Candeloro De Sanctis, Sofia, Caracciolo, Giulio
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Animals
Cell Membrane - chemistry
Chemistry
Colloidal state and disperse state
Colloids: Surfactants and Self-Assembly, Dispersions, Emulsions, Foams
DNA - chemistry
Exact sciences and technology
Fibroblasts - chemistry
Fibroblasts - cytology
Gene Transfer Techniques
General and physical chemistry
Lipids - chemistry
Liposomes - chemical synthesis
Liposomes - chemistry
Membranes
Mice
Particle Size
Surface Properties
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Summary:The first interaction between lipoplexes and cells is charge-mediated and not specific. Endocytosis is considered to be the main pathway for lipoplex entry. Upon interaction between lipoplexes and the plasma membrane, intermixing between lipoplex and membrane lipids is necessary for efficient endocytosis. Here we study the mechanism of the different endocytic pathways in lipid-mediated gene delivery. We show that DC−Chol−DOPE/DNA lipoplexes preferentially use a raft-mediated endocytosis, while DOTAP−DOPC/DNA systems are mainly internalized by not specific fluid phase macropinocitosys. On the other hand, most efficient multicomponent lipoplexes, incorporating different lipid species in their lipid bilayer, can use multiple endocytic pathways to enter cells. Our data demonstrate that efficiency of endocytosis is regulated by shape coupling between lipoplex and membrane lipids. We suggest that such a shape-dependent coupling regulates efficient formation of endocytic vesicles thus determining the success of internalization. Our results suggest that tailoring the lipoplex lipid composition to the patchwork-like plasma membrane profile could be a successful machinery of coordinating the endocytic pathway activities and the subsequent intracellular processing.
ISSN:0743-7463
1520-5827
DOI:10.1021/la1023899