title: Direct observation of dynamic mechanical regulation of DNA condensation by environmental stimuli.
abstract: Gene delivery is a promising way to treat hereditary diseases and cancer; however, there is little understanding of DNA:carrier complex mechanical properties, which may be critical for the protection and release of nucleic acids. We applied optical tweezers to directly measure single-molecule mechanical properties of DNA condensed using 19-mer poly-L-lysine (PLL) or branched histidine-lysine (HK) peptides. Force-extension profiles indicate that both carriers condense DNA actively, showing force plateaus during stretching and relaxation cycles. As the environment such as carrier concentration, pH, and the presence of zinc ions changes, DNA:HK complexes showed dynamically regulated mechanical properties at multiple force levels. The fundamental knowledge from this study can be applied to design a mechanically tailored complex which may enhance transfection efficiency by controlling the stability of the complex temporally and spatially.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742 (USA).
authors.forename: Amy
authors.initials: A
authors.lastname: Lee
authors.forename: Adam
authors.initials: A
authors.lastname: Karcz
authors.forename: Ryan
authors.initials: R
authors.lastname: Akman
authors.forename: Tai
authors.initials: T
authors.lastname: Zheng
authors.forename: Sara
authors.initials: S
authors.lastname: Kwon
authors.forename: Szu-Ting
authors.initials: ST
authors.lastname: Chou
authors.forename: Sarah
authors.initials: S
authors.lastname: Sucayan
authors.forename: Lucas J
authors.initials: LJ
authors.lastname: Tricoli
authors.forename: Jason M
authors.initials: JM
authors.lastname: Hustedt
authors.forename: Qixin
authors.initials: Q
authors.lastname: Leng
authors.forename: Jason D
authors.initials: JD
authors.lastname: Kahn
authors.forename: A James
authors.initials: AJ
authors.lastname: Mixson
authors.forename: Joonil
authors.initials: J
authors.lastname: Seog
mesh_terms: D000595:Amino Acid Sequence; D002413:Cations, Divalent / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006639:Histidine; D008239:Lysine / Q000737:chemistry; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D052898:Optical Tweezers; D010455:Peptides / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
chemical_list: D002413:Cations, Divalent; D010455:Peptides; D011107:Polylysine; D006639:Histidine; D004247:DNA; D015032:Zinc; D008239:Lysine
keywords: DNA condensation; cationic peptides; gene delivery; optical tweezers; single-molecule studies