Terahertz-Driven Conformational Remodeling of Filamentous Actin: Insights into Intense Terahertz-Field-Mediated Biopolymer Responses
Chang Liu, Baolong Zhang, Chaojing Shi, Guoqian Liao, Yanyu Wei, Jinglong Ma, Ziyang Ma, Jiangrui Zhu, Zhaoyu Li, Chutong Gao, Yaqun Zhang, Rao Fu, Xiaorui Huang, Ying Liu, Feng Qi, Fangfu Ye, QianJin Guo, Jianing Chen, Xiaojun Wu, Ming Li, Weihai Fang, Yutong Li, Yunliang LiAbstract
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.