A Control Chetaev Function-Based Approach for Unfolding of Proteins at the Single-Molecule Level via Optical Tweezers

Abstract This article investigates the closed-loop control of protein unfolding at the single-molecule level in optical tweezers through a control Chetaev function (CCF) framework. Unlike earlier approaches that focus mainly on stabilizing particle positions, our method leverages CCFs as the framework for regulating protein unfolding in real time. This formulation, which offers robustness in the presence of nonlinear dynamics and external disturbances, provides a control-theoretic basis for feedback strategies in biomolecule unfolding. Simulations on the protein Barnase show that the proposed CCF-based controller can reliably drive unfolding to a contour length of approximately 28 nm within 0.5 ms, while maintaining the trap focus within a bound of 60 nm and limiting the applied force across sampling rates of 5–50 kHz.