Direct Observation of Dynamic Mechanical Regulation of DNA Condensation by Environmental Stimuli

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 mechan...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2014-09, Vol.53 (40), p.10631-10635
Main Authors: Lee, Amy, Karcz, Adam, Akman, Ryan, Zheng, Tai, Kwon, Sara, Chou, Szu-Ting, Sucayan, Sarah, Tricoli, Lucas J., Hustedt, Jason M., Leng, Qixin, Kahn, Jason D., Mixson, A. James, Seog, Joonil
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Branched
Carrier density
Carriers
cationic peptides
Cations, Divalent - chemistry
Condensation
Condensing
Deoxyribonucleic acid
DNA
DNA - administration & dosage
DNA - chemistry
DNA condensation
gene delivery
Gene Transfer Techniques
Histidine
Lysine - chemistry
Mechanical properties
Molecular Sequence Data
Nucleic Acid Conformation
Optical Tweezers
Peptides
Peptides - chemistry
Polylysine - chemistry
single-molecule studies
Zinc
Zinc - chemistry
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Summary: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. Optical tweezers were used 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. As the carrier concentration, pH, and the presence of zinc ions changes, DNA:HK complexes showed dynamically regulated mechanical properties at multiple force levels.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201403499