Turning angle analysis reveals hidden anisotropies in the anomalous diffusion of molecules in live cells

Abstract

Molecular motion within living cells provides a window into the physical principles underlying intracellular organization and transport. Yet a fundamental limitation remains: measured trajectories are often short, noisy, and randomly oriented, rendering spatial anisotropies inaccessible to conventional analyses. We show that turning-angle statistics provide a robust approach for uncovering anisotropies in anomalous diffusion. Using a two-dimensional anisotropic fractional Brownian motion model with random orientations, we show theoretically and through simulations that turning-angle distributions preserve signatures of anisotropy. We apply this approach to single-particle tracking data, including quantum dots in the cytoplasm of HeLa cells and membrane proteins in hippocampal neurons. Turning angles reveal hidden anisotropies in the motion of quantum dots and Nav 1.6 channels, and in specific dynamical states of glycoprotein CD4. These results establish turning-angle analysis as a powerful strategy for detecting organization in complex environments and reveal that anisotropic anomalous diffusion is an overlooked feature of intracellular dynamics.