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Revealing Three Stages of DNA-Cisplatin Reaction by a Solid-State Nanopore.

Zhou Z, Hu Y, Shan X, Li W, Bai X, Wang P, Lu X - Sci Rep (2015)

Bottom Line: The interaction processes are found to be well elucidated by the evolution of the capture rate of DNA-cisplatin complex, which is defined as the number of their translocation events through the nanopore in unit time.In the second stage, by forming di-adducts, the capture rate increases as DNA molecules are softened, appears as the reduced persistence length of the DNA-cisplatin adducts.In the third stage, the capture rate decreases again as a result of DNA aggregation.

View Article: PubMed Central - PubMed

Affiliation: Beijing National Laboratory for Condensed-Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.

ABSTRACT
The dynamic structural behavior in DNA due to interaction with cisplatin is essential for the functionality of platinum-based anti-cancer drugs. Here we report a novel method to monitor the interaction progress in DNA-cisplatin reaction in real time with a solid-state nanopore. The interaction processes are found to be well elucidated by the evolution of the capture rate of DNA-cisplatin complex, which is defined as the number of their translocation events through the nanopore in unit time. In the first stage, the capture rate decreases rapidly due to DNA discharging as the positive-charged hydrated cisplatin molecules initially bond to the negative-charged DNA and form mono-adducts. In the second stage, by forming di-adducts, the capture rate increases as DNA molecules are softened, appears as the reduced persistence length of the DNA-cisplatin adducts. In the third stage, the capture rate decreases again as a result of DNA aggregation. Our study demonstrates a new single-molecule tool in exploring dynamic behaviors during drug-DNA reactions and may have future application in fast drug screening.

No MeSH data available.


(a) Typical current trace with translocation events of DNA-cisplatin adducts through a SiN nanopore. The pore diameter is 5.8 nm and the driving voltage is 500 mV. (b) Histogram distribution of time interval δt between adjacent events. The red curve is the exponential fit with capture rate of 1.59 ± 0.07 s−1. (c) Evolution of capture rate as a function of reaction time. The red curve and the colored background are guided for the eye.
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f2: (a) Typical current trace with translocation events of DNA-cisplatin adducts through a SiN nanopore. The pore diameter is 5.8 nm and the driving voltage is 500 mV. (b) Histogram distribution of time interval δt between adjacent events. The red curve is the exponential fit with capture rate of 1.59 ± 0.07 s−1. (c) Evolution of capture rate as a function of reaction time. The red curve and the colored background are guided for the eye.

Mentions: Figure 2a presents a typical current trace with translocation events of DNA-cisplatin adducts, in which the relative ratio α equals 0.5. The translocation events are represented by the spikes in the trace. The time interval between adjacent events, δt, is statistically analyzed with the histogram plot, as shown in Fig. 2b. The distribution can be fitted with an exponential function, P(δt) = N * exp(−J * δt), where N is a normalization constant and J is the capture rate which is of our main interest29. Fitting the data in Fig. 2b derives a capture rate of 1.59 ± 0.07 s−1 (events per second). To investigate the dynamic progress of DNA-cisplatin interaction, the temporal variation in capture rate is measured as a function of reaction time. Figure 2c shows the evolution of the capture rate along a period of 25 hours for a 5.8 nm nanopore. Three stages are clearly illustrated. The capture rate reduces rapidly in the first a few hours (stage I), it then increases to a saturated value in the following 10 hours or so (stage II), and decreases again (stage III). Such feature is observed for all experiments with α varies from 0.5 up to 10. The characteristic feature in capture rate reflects different dynamic behaviors in each stage: DNA discharging, DNA softening, and DNA aggregation, as we explain in details in the following sections.


Revealing Three Stages of DNA-Cisplatin Reaction by a Solid-State Nanopore.

Zhou Z, Hu Y, Shan X, Li W, Bai X, Wang P, Lu X - Sci Rep (2015)

(a) Typical current trace with translocation events of DNA-cisplatin adducts through a SiN nanopore. The pore diameter is 5.8 nm and the driving voltage is 500 mV. (b) Histogram distribution of time interval δt between adjacent events. The red curve is the exponential fit with capture rate of 1.59 ± 0.07 s−1. (c) Evolution of capture rate as a function of reaction time. The red curve and the colored background are guided for the eye.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493569&req=5

f2: (a) Typical current trace with translocation events of DNA-cisplatin adducts through a SiN nanopore. The pore diameter is 5.8 nm and the driving voltage is 500 mV. (b) Histogram distribution of time interval δt between adjacent events. The red curve is the exponential fit with capture rate of 1.59 ± 0.07 s−1. (c) Evolution of capture rate as a function of reaction time. The red curve and the colored background are guided for the eye.
Mentions: Figure 2a presents a typical current trace with translocation events of DNA-cisplatin adducts, in which the relative ratio α equals 0.5. The translocation events are represented by the spikes in the trace. The time interval between adjacent events, δt, is statistically analyzed with the histogram plot, as shown in Fig. 2b. The distribution can be fitted with an exponential function, P(δt) = N * exp(−J * δt), where N is a normalization constant and J is the capture rate which is of our main interest29. Fitting the data in Fig. 2b derives a capture rate of 1.59 ± 0.07 s−1 (events per second). To investigate the dynamic progress of DNA-cisplatin interaction, the temporal variation in capture rate is measured as a function of reaction time. Figure 2c shows the evolution of the capture rate along a period of 25 hours for a 5.8 nm nanopore. Three stages are clearly illustrated. The capture rate reduces rapidly in the first a few hours (stage I), it then increases to a saturated value in the following 10 hours or so (stage II), and decreases again (stage III). Such feature is observed for all experiments with α varies from 0.5 up to 10. The characteristic feature in capture rate reflects different dynamic behaviors in each stage: DNA discharging, DNA softening, and DNA aggregation, as we explain in details in the following sections.

Bottom Line: The interaction processes are found to be well elucidated by the evolution of the capture rate of DNA-cisplatin complex, which is defined as the number of their translocation events through the nanopore in unit time.In the second stage, by forming di-adducts, the capture rate increases as DNA molecules are softened, appears as the reduced persistence length of the DNA-cisplatin adducts.In the third stage, the capture rate decreases again as a result of DNA aggregation.

View Article: PubMed Central - PubMed

Affiliation: Beijing National Laboratory for Condensed-Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.

ABSTRACT
The dynamic structural behavior in DNA due to interaction with cisplatin is essential for the functionality of platinum-based anti-cancer drugs. Here we report a novel method to monitor the interaction progress in DNA-cisplatin reaction in real time with a solid-state nanopore. The interaction processes are found to be well elucidated by the evolution of the capture rate of DNA-cisplatin complex, which is defined as the number of their translocation events through the nanopore in unit time. In the first stage, the capture rate decreases rapidly due to DNA discharging as the positive-charged hydrated cisplatin molecules initially bond to the negative-charged DNA and form mono-adducts. In the second stage, by forming di-adducts, the capture rate increases as DNA molecules are softened, appears as the reduced persistence length of the DNA-cisplatin adducts. In the third stage, the capture rate decreases again as a result of DNA aggregation. Our study demonstrates a new single-molecule tool in exploring dynamic behaviors during drug-DNA reactions and may have future application in fast drug screening.

No MeSH data available.