Terahertz-Driven Conformational Remodeling of Filamentous Actin: Insights into Intense Terahertz-Field-Mediated Biopolymer Responses

We demonstrate the precise, noninvasive control of filamentous actin (F-actin) conformations using high-intensity terahertz (THz) pulses via a dominantly nonthermal mechanism. By combining femtosecond time-resolved mid-infrared spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, super-resolution confocal imaging, and a data-driven machine learning pipeline (CNN–UMAP–K-means), we show that 0.4 THz pulses selectively weaken intermolecular β-sheet structures (1615 cm–1) while enhancing α-helical content (1650 cm–1) in F-actin, driving a dynamical shift toward monomer-like (G-actin) vibrational energy relaxation (VER) with up to 95% spectral similarity. In A549 cells, THz irradiation systematically reduces F-actin aggregation, as evidenced by fluorescence imaging. The spectral and dynamical changes induced by THz differ distinctly from thermal denaturation, with no characteristic peak shift observed under heating, supporting a dominantly nonthermal mechanism; our observations are consistent with coupling between intense terahertz fields and collective low-frequency intermonomer vibrational motions within F-actin filaments. The machine learning framework enables unbiased clustering and quantitative similarity analysis to identify optimal irradiation parameters (70 μJ, 10 min) that maximize selective F-actin remodeling without perturbing G-actin integrity. This work establishes intense THz as a powerful photonic tool for manipulating protein assemblies at molecular and cellular levels, advancing our fundamental understanding of THz–biopolymer interactions for biophotonic applications.