Label-Free Free-Solution Single-Molecule Protein–Small Molecule Interaction Observed by Double-Nanohole Plasmonic Trapping

Abstract

The interaction of proteins with small molecules is fundamental to their function in living organisms and it is widely studied in drug development. Here we compare optical trapping dynamics of streptavidin and biotinylated streptavidin using a double nanohole optical trap in a metal film. Consistent and clearly distinct behavior is seen between the protein with and without the small molecule binding. The real-time dynamics at the single protein level are accessible with this technique, which also has advantages of not requiring tethering to a surface or the need for exogeneous markers.Protein-small molecule interactions (PSMIs) play an important role in biological functions. PSMIs are also of primary interest for the development of drugs, for example through inhibition of protein interactions. 1 While many works have studied PSMIs, only few approaches

Advances in optoplasmonic sensors – combining optical nano/microcavities and photonic crystals with plasmonic nanostructures and nanoparticles

“…Interesting and promising features for biosensing were also shown for optical traps such as double nanohole structures ( Figure 2M) [34,[45][46][47][48][49]. The specific structure of the double nanoholes results in an optical tweezer that can trap and simultaneously sense single biomolecules in a label-free manner [46].…”

“…(M) SEM image of a Au double nanohole used to trap and sense single biomolecules. Adapted from [34].…”

Characterization of the near-field and convectional transport behavior of micro and nanoparticles in nanoscale plasmonic optical lattices

“…[7][8][9][10] In liquid environments, these efforts have culminated in the recent demonstration of the tweezing of a single protein molecule and measurement of mechanical vibration to reveal its identity with the extraordinary acoustic Raman technique. [11][12][13][14][15] Technical advances in conventional optical trapping techniques have enabled the creation of microscale and nanoscale one-, two-, and three-dimensional periodic potentials (or optical lattices). [16][17][18] Using such techniques and by leveraging the principle of optical fractionation in microfluidic environments, optical sorting by particle size or index of refraction has been demonstrated.…”

Nano-bio-optomechanics: nanoaperture tweezers probe single nanoparticles, proteins, and their interactions

“…The ability to trap single proteins has allowed for studying protein-antibody binding [17], protein-DNA interactions [15], protein sizing [18], protein-protein interactions [18], protein small-molecule interactions (both in the strong binding [19] and weak binding limits [20]). In typical studies, the aperture transmission is used to monitor light scattering changes by the protein or DNA particles, thereby giving direct information about their structure (via their diffractive properties).…”

“…Not only is it possible to see directly if a small molecule is binding to a protein (through changes in the fluctuations of the optical transmission through the aperture -representing thermal motion of the particle) [19], but it is also possible to monitor on-off binding kinetics to determine the binding affinity [20]. In this way, potential small molecule drug candidates can be probed for their interactions with proteins.…”