| Résumé: | <p>Measurement of molecular properties at the single-molecule level can reveal valuable information, often hidden in ensemble measurements. In this Thesis, we present a range of novel high-precision molecular measurements in solution enabled by the electrostatic fluidic trapping approach.</p>
<p>The working principle of an electrostatic fluidic trap relies on the equilibrium thermodynamic repulsion experienced by a charged object confined in a fluidfilled gap between two like-charged surfaces. Geometric tailoring of one of the surfaces by nanostructured surface indentations reduces interaction energy, creating an electrostatic potential well capable of stable trapping of a charged object in solution. The ability of a recently developed escape-time electrometry (ETe) technique to precisely measure the depth of potential well underlies the high-precision measurement of effective electrical charge, qeff, of a trapped molecule.</p>
<p>In the original work, upon which this Thesis is based, we first focus on expanding the capabilities of the electrostatic fluidic trapping approach. We demonstrate the ability of stable trapping in a range of solvents of different polarities and present a novel approach for measuring the net surface charge at the solid-liquid interface. We further explore the applicability of charged lipid bilayer systems for single-molecule electrostatic trapping and describe how chemical composition of nanostructured supported lipid bilayers can be measured by means of ETe.</p>
<p>We finally demonstrate the ability to use the qeff of a biomolecule in solution to infer key details of its atomic level structure. Performing ETe measurements on A- and B-form (RNA and DNA) double helixes, we achieve a ∼ 1Å and ∼ 0.1Å precision on the helical radius and rise per basepair, respectively. Moreover, in conjunction with a recently developed theoretical approach to model electrostatics of biomolecules in solution, our examination of structural parameters provides an unprecedented new view of the molecule-solvent interface.</p>
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