Temperature-controlled nanoaperture optical trapping

Date

2025

Authors

Letwin, Keiran

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Abstract

Nanoaperture optical trapping (NOT) enables the capture of single proteins to detect their conformational dynamics without labeling or tethering, thus preserving their structure. Protein folding is highly sensitive to environmental conditions, making the investigation of thermodynamic parameters a robust method for probing conformational stability. While previous studies have employed laser-induced heating to modulate the local temperature, such methods are limited in accessing broader temperature ranges. In this work, the low-temperature dynamics of individual Bovine Serum Albumin (BSA) are investigated using a custom-built temperature-controlled stage. The transitions between the normal (N) and fast (F) conformational states of BSA were uncovered. Notably, the N form exhibited a maximum occupancy at \(21 \pm 1\,^{\circ}\mathrm{C}\), which was interpreted as the point of maximal thermodynamic stability for the compact N state relative to the F state. This approach enabled the extraction of single-molecule thermodynamic parameters without requiring modification to the protein's native structure, providing a multifaceted NOT method for broad applications.

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Keywords

Nanoaperture optical trapping, Protein conformational dynamics, Label-free, Thermodynamic, Temperature-controlled

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