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Sensing Single Molecule Penetration into Nanopores: Pushing the Time Resolution to the Diffusion Limit
Igor V Bodrenko1, Jiajun Wang2, Samuele Salis1
1Department of Physics, University of Cagliari , S.P. Monserrato-Sestu km 0.700, I-09042, Monserrato, Cagliari, Italy.
ACS Sensors
|July 22, 2017
Summary
We developed a new method to measure how quickly small molecules enter and exit nanopores. This technique accurately quantifies the fast interactions of molecules like the antibiotic Meropenem with bacterial channels.
Area of Science:
- Biophysics
- Nanotechnology
- Pharmacology
Background:
- Quantifying molecular transport through nanopores is crucial for understanding biological processes and developing new drug delivery systems.
- Existing methods often lack the resolution to capture rapid molecular interactions within nanopores.
- Bacterial outer membrane channels, like OmpF, are key targets for antibiotics but their precise interaction dynamics with drugs remain challenging to study.
Purpose of the Study:
- To develop and validate an improved excess-noise analysis technique for quantifying small molecule kinetics in nanopores.
- To determine the kinetic parameters of substrate entry and exit using a two-state Markov model.
- To apply this method to study the interaction of Meropenem with the OmpF channel.
Main Methods:
- Applied improved excess-noise analysis of ion current fluctuations caused by molecule entry.
- Utilized a two-state Markov model to derive kinetic parameters from ion current and variance.
- Incorporated filter corrections to extend detectable transition rates beyond instrumental cutoff frequencies.
- Analyzed single-channel ion current of Meropenem interacting with OmpF at 40°C.
Main Results:
- Successfully quantified small molecule penetration and permeation through nanopores.
- Derived kinetic parameters for substrate entry and exit, including residence time.
- Determined the residence time of Meropenem within the OmpF channel to be approximately 500 ns.
- Demonstrated that submicrosecond-scale gating kinetic parameters are accessible with current experimental setups.
Conclusions:
- The improved excess-noise analysis method enables precise quantification of rapid molecular interactions in nanopores.
- The technique accurately measures residence times, even those close to the diffusion limit.
- This approach provides a powerful tool for studying antibiotic-channel interactions and other molecular transport phenomena.
- Submicrosecond kinetic parameters of channel gating are experimentally accessible, opening new avenues for research.
