Single Molecule Translocation through Biological Nanopores with Optical Tweezers

• Applicant: Professor Dr. Dario Anselmetti
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics ; Biophysics
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 269589970

In the proposed research project we plan to use optical tweezers force mechanics to investigate and quantify the translocation mechanisms and dynamics of single biopolymers through biological nanopores (biopores) with (sub)molecular resolution. This single molecule technology allows to measure effective molecular forces and elasticities, mechanical noise spectra, translocation dynamics, associated energy landscape as well as associated nanofluidic properties without molecule labelling and amplification. We will study how chain-like macromolecules like nucleic acids, polysaccharides, as well as folded and unfolded proteins will be threaded through biopores (porins) that are functionally integrated in supported biomembranes and biomimetic lipid-hybrids thereof, combining manifold aspects of single-molecule force spectroscopy with nanofluidics. Since single-molecule translocation is governed by thermal non-equilibrium, fast thermal fluctuations and macromolecular stochastics, we aim for a fast force and noise analysis together with a coherent description of the experimental results with stochastic simulations (Cooperation: P. Reimann). We aim for deep fundamental mechanistic insights into the molecule translocation through biopores in general, as well as nanobiotechnological applications thereof. The latter rely on the identification of specific, sub-molecular force signatures during translocation through biological nanopores, allowing to deduce structural information of the translocated macromolecule (e.g. the methylation pattern of DNA).

• DFG Programme: Research Grants
• Cooperation Partner: Professor Dr. Peter Reimann