title: Tailoring lipoplex composition to the lipid composition of plasma membrane: a Trojan horse for cell entry?
abstract: 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.
authors.affiliation: Department of Bioscience and Biotechnology, University of Camerino, Via Gentile III da Varano, 62032 Camerino (MC), Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Marchini
authors.forename: Daniela
authors.initials: D
authors.lastname: Pozzi
authors.forename: Maura
authors.initials: M
authors.lastname: Montani
authors.forename: Cinzia
authors.initials: C
authors.lastname: Alfonsi
authors.forename: Augusto
authors.initials: A
authors.lastname: Amici
authors.forename: Heinz
authors.initials: H
authors.lastname: Amenitsch
authors.forename: Sofia
authors.initials: S
authors.lastname: Candeloro De Sanctis
authors.forename: Giulio
authors.initials: G
authors.lastname: Caracciolo
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology*; D018014:Gene Transfer Techniques; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry*; D051379:Mice; D010316:Particle Size; D013499:Surface Properties
chemical_list: D008055:Lipids; D008081:Liposomes; D004247:DNA