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ABSTRACT: The nanopore sensor, consisting of an individual pore with diameter of few nanometers, can detect the shape and the structure of many individual biopolymers. Combining single-molecule detection with a high-throughput, it allows us to explore rare structures in biopolymers, sometimes with atomic precision. The nanopores have been employed for DNA sequencing, protein fingerprinting, and virus detection.
We employed a new nanopore-based technique to precisely analyse the knotting of long DNA chains in equilibrium, and to explore the dynamics of knots in single digit nanopores. We showed that DNA becomes malleable in nanoscale constrictions at short timescales, and capable of sharp buckling beyond the limit of the standard polymer model. By precisely quantifying the DNA knotting probability – which is a very sensitive measure of the inter-DNA interactions – we observed onset of inter-DNA attraction moderated by monovalent ions at high concentration. Strong DNA attraction has been observed in the past for multivalent ions, but never for monovalent ions due to a lack of instrumental techniques that could quantify moderate interactions.
Our results are relevant not only for the understanding of DNA packing and manipulation in living cells, but also for the development of nanopore-based sequencing technologies. As we strive to employ synthetic biological machinery in different environments, unshackled from physiology, understanding inter-DNA interaction at high molarity becomes even more so biotechnologically important.
BIOGRAPHY: Slaven Garaj's research is focused on curious nanoscale phenomena at the interfaces between soft and hard matter, with particular interest in nanopores single-molecule sensors, nano-fluidics and nano-electronics. His research has been features in top journals such as Nature, Science, Nature sister journals, and PNAS, and received a keen attention in the media. While pursuing in-depth scientific understanding, his research group drives the development of technologies in the fields of medical diagnostics, water filtration and energy harvesting. His patents are licensed by biotech companies, and he is a founder of cleantech start-up company ReActo, focused on removing persistent contaminants from water.
Prof. Slaven Garaj joined National University of Singapore in 2012 as faculty member in the Departments of Physics and Biomedical Engineering, and has been awarded NRF Fellowship. Previously, he worked as a research scientist at Harvard University, where he pioneered work on 2D nanopores for DNA sequencing. He conducted his PhD thesis at the Swiss Federal Institute of Technology in Lausanne (EPFL), Switzerland in the field of condensed-matter physics.