Transient Cytoskeletal Anisotropy Encodes Short‐Term Mechanical Memory in Glioblastoma Cells

Abstract

ABSTRACT Cells experience time‐varying mechanical cues when navigating complex microenvironments, yet whether and how they retain a short‐term memory of recent deformations remains unclear. Here, we show that glioblastoma cells encode such memory through transient cytoskeletal anisotropy. Combining magneto‐mechanical actuation, nanoindentation, and selective cytoskeletal perturbations, we find that actin architectures drive opposite mechanical responses: stress fibers stiffen cells under stretch, whereas the actin cortex governs softening under compression. Vimentin intermediate filaments stabilize actin organization under load, preserving these deformation‐specific responses. Mechanical actuation aligns both networks, more strongly for actin than vimentin, and this anisotropy persists after unloading. Using a two‐step actuation protocol, we show that residual alignment biases the response to a second deformation: cells retain information about prior loading, and this bias decays as the cytoskeleton relaxes, defining a memory window of minutes to tens of minutes. To integrate these observations, we develop a multi‐network constitutive model that links cytoskeletal architecture and loading history to cell mechanics, reproducing asymmetric mechanical responses, cytoskeletal reorganization dynamics, and memory effect. These findings show how invasive cancer cells could exploit residual cytoskeletal order to adapt to fluctuating solid stresses and confinement, and identify vimentin–actin coupling and remodeling kinetics as levers to limit that adaptability.