Multiscale mechanics and temporal evolution of vimentin intermediate filament networks

Significance The mechanical integrity of cells and their ability to adapt—for example, during wound healing or in metastasizing tumors—is largely determined by the cytoskeleton. The cytoskeleton is an intricate network of biopolymers and cross-linkers. Intermediate filaments, the softest and most extensible of the three filamentous proteins of the cytoskeleton, take the role of a safety belt for cells under strain. The mechanical properties of a network depend on several factors, such as the length and mechanical properties of the single filaments and, importantly, the interactions between filaments. Here, we use a multiscale approach to disentangle these effects, which allows for direct quantification of interaction kinetics. The cytoskeleton, an intricate network of protein filaments, motor proteins, and cross-linkers, largely determines the mechanical properties of cells. Among the three filamentous components, F-actin, microtubules, and intermediate filaments (IFs), the IF network is by far the most extensible and resilient to stress. We present a multiscale approach to disentangle the three main contributions to vimentin IF network mechanics—single-filament mechanics, filament length, and interactions between filaments—including their temporal evolution. Combining particle tracking, quadruple optical trapping, and computational modeling, we derive quantitative information on the strength and kinetics of filament interactions. Specifically, we find that hydrophobic contributions to network mechanics enter mostly via filament-elongation kinetics, whereas electrostatics have a direct influence on filament–filament interactions.