Abstract
The natural vibrational frequencies of biological particles such as viruses and bacteria encode critical information about their mechanical and biological states as they interact with their local environment and undergo structural evolution. However, detecting and tracking these vibrations within a biological context at the single particle level has remained elusive. In this study, we track the vibrational motions of single, unlabeled virus particles under ambient conditions using ultrafast spectroscopy. The ultrasonic spectrum of an 80 to 100 nm lentiviral pseudovirus reveals vibrational modes in the 19 to 21 GHz range sensitive to virus morphology and 2 to 10 GHz modes with nanosecond dephasing times reflecting viral envelope protein interactions. By tracking virus trajectories over minutes, we observe acoustic mode coupling mediated by the local environment. Single particle tracking allows the capture of viral disassembly through correlated mode softening and dephasing. The sensitivity, high resolution, and speed of this approach promise deeper insights into biological dynamics and early-stage diagnostics at the single microorganism level.