Electrostatic free energies carry structural information on nucleic acid molecules in solution

Journal article

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. 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. 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. 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

Authors: Behjatian, A; Krishnan, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Institute of Physics
• Journal: The Journal of Chemical Physics
• Volume: 156
• Issue: 13
• Pages: 134201-134201
• Article number: 134201
• Publication date: 2022-04-01
• DOI: 10.1063/5.0080008
• EISSN: 1089-7690
• ISSN: 0021-9606
• Language: English
• Keywords: Chemical physics; Counterion; Nucleic acid; Crystallography; Biomolecule; RADIUS; Helix (gastropod); Static electricity; Physics; Molecular physics; Molecule; Chemistry; Physical chemistry; Ion; Electrostatics