Seham Helmi

Abstract:

Label-free detection of single biomolecules in solution has been achieved using a variety of experimental approaches over the past decade. Yet, our understanding of the magnitude of the optical contrast and its relationship with the underlying atomic structure as well as the achievable measurement sensitivity and precision remain poorly defined. Here, we use a Fourier optics approach combined with an atomic structure-based molecular polarizability model to simulate mass photometry experiments from first principles. We find excellent agreement between several key experimentally determined parameters such as optical contrast-to-mass conversion, achievable mass accuracy, and molecular shape and orientation dependence. This allows us to determine detection sensitivity and measurement precision mostly independent of the optical detection approach chosen, resulting in a general framework for light-based single-molecule detection and quantification.

Abstract:

Nanoscience aspires to mimic nature's control over functional molecular assemblies. Here we present a templating technique for the efficient attachment of two different oligonucleotides to a homobifunctional molecule, enabling its controlled and programmable placement within a DNA nanostructure. We demonstrate its application to a range of organic molecules with different conjugation chemistries and water solubilities. We show that the two oligonucleotide adapters can be used to integrate a bifunctional cyanine dye into a self-assembled 3D-DNA origami nanostructure, giving control of both position and orientation. We also demonstrate the use of both adapters to exert dynamic control over the environment of the target molecule by means of a series of strand-displacement reactions.