Project description
Measuring electric forces between biological molecules and their environment
Opposite charges attract, while like charges repel each other. This is easy enough to see and measure in a simple high school physics experiment using balloons and static electricity. It is much more difficult when it comes to charged biological molecules in their natural environment, physiological saline, that consists of polar water molecules and positively charged ions. The EU-funded BIOVIB project will take an unprecedented closer look at hydrated RNA and DNA molecules. By harnessing multidimensional vibrational spectroscopy and externally applied THz electric fields, scientists plan to open a new window on the electric forces pulling and pushing biological molecules and stabilising their structure.
Objective
Biomolecules exist in an aqueous environment of dipolar water molecules and solvated ions. Their structure and biological function are strongly influenced by electric interactions with the fluctuating water shell and ion atmosphere. Understanding such interactions at the molecular level is a major scientific challenge; presently, their strengths, spatial range and interplay with other non-covalent interactions are barely known. Going far beyond existing methods, this project introduces the new paradigm of a direct time-resolved mapping of molecular electric forces on sub-nanometer length scales and at the genuine terahertz (THz) fluctuation frequencies. Vibrational excitations of biomolecules at the interface to the water shell act as sensitive noninvasive probes of charge dynamics and local electric fields. The new method of time resolved vibrational Stark shift spectroscopy with THz external fields calibrates vibrational frequencies as a function of absolute field strength and separates instantaneous from retarded environment fields. Based on this knowledge, multidimensional vibrational spectroscopy gives quantitative insight in the biomolecular response to electric fields, discerning contributions from water and ions in a site-specific way. The experiments and theoretical analysis focus on single- and double-stranded RNA and DNA structures at different hydration levels and with ion atmospheres of controlled composition, structurally characterized by x-ray scattering. As a ground-breaking open problem, the role of magnesium and other ions in RNA structure definition and folding will be addressed by following RNA folding processes with vibrational probes up to milliseconds. The impact of site-bound versus outer ions will be dynamically separated to unravel mechanisms stabilizing secondary and tertiary RNA structures. Beyond RNA research, the present approach holds strong potential for fundamental insight in transmembrane ion channels and channel rhodopsins.
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Funding Scheme
ERC-ADG - Advanced GrantHost institution
12489 Berlin
Germany