title: Patterned Threadlike Micelles and DNA-Tethered Nanoparticles: A Structural Study of PEGylated Cationic Liposome-DNA Assemblies.
abstract: The self-assembly of oppositely charged biomacromolecules has been extensively studied due to its pertinence in the design of functional nanomaterials. Using cryo electron microscopy (cryo-EM), optical light scattering, and fluorescence microscopy, we investigated the structure and phase behavior of PEGylated (PEG: poly(ethylene glycol)) cationic liposome-DNA nanoparticles (CL-DNA NPs) as a function of DNA length, topology (linear and circular), and ρ(chg) (the molar charge ratio of cationic lipid to anionic DNA). Although all NPs studied exhibited lamellar internal nanostructure, NPs formed with short (∼2 kbps), linear, polydisperse DNA were defect-rich and contained smaller domains. Unexpectedly, we found distinctly different equilibrium structures away from the isoelectric point. At ρ(chg) > 1, in the excess cationic lipid regime, threadlike micelles rich in PEG-lipid were found to coexist with NPs, cationic liposomes, and spherical micelles. At high concentrations these PEGylated threadlike micelles formed a well-ordered, patterned morphology with highly uniform intermicellar spacing. At ρ(chg) < 1, in the excess DNA regime and with no added salt, individual NPs were tethered together via long, linear DNA (48 kbps λ-phage DNA) into a biopolymer-mediated floc. Our results provide insight into what equilibrium nanostructures can form when oppositely charged macromolecules self-assemble in aqueous media. Self-assembled, well-ordered threadlike micelles and tethered nanoparticles may have a broad range of applications in bionanotechnology, including nanoscale lithograpy and the development of lipid-based multifunctional nanoparticle networks.
authors.affiliation: †Department of Physics, Department of Materials, and Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, California 93106, United States.
authors.forename: Ramsey N
authors.initials: RN
authors.lastname: Majzoub
authors.affiliation: †Department of Physics, Department of Materials, and Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, California 93106, United States.
authors.forename: Kai K
authors.initials: KK
authors.lastname: Ewert
authors.affiliation: ‡National Resource for Automated Molecular Microscopy, Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Jacovetty
authors.affiliation: ‡National Resource for Automated Molecular Microscopy, Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Bridget
authors.initials: B
authors.lastname: Carragher
authors.affiliation: ‡National Resource for Automated Molecular Microscopy, Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Clinton S
authors.initials: CS
authors.lastname: Potter
authors.affiliation: §Materials Research Laboratory, University of California, Santa Barbara, California 93106, United States.
authors.forename: Youli
authors.initials: Y
authors.lastname: Li
authors.affiliation: †Department of Physics, Department of Materials, and Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, California 93106, United States.
authors.forename: Cyrus R
authors.initials: CR
authors.lastname: Safinya
mesh_terms: D004247:DNA / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D008081:Liposomes; D008823:Micelles; D011092:Polyethylene Glycols; D004247:DNA