Probing F-actin Stability and Mechanics using Structure-Based Computational Modeling

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Filamentous actin (F-actin) is a core component of the cytoskeleton that is active in both homeostatic and dynamic cellular processes and interacts with a broad range of actin-binding proteins that regulate its stability, higher-order structure, and mechanical properties. Recent structural studies utilizing cryo-electron microscopy and 3D particle reconstruction have provided novel structural models of F-actin in isolation as well as with various bound actin-binding proteins, offering new opportunities to understand the molecular basis of F-actin stability and mechanics. Here we apply a recently introduced computational framework based on the finite element method to model the bending, twisting, and stretching deformation of 150 nm F-actin in experimentally observed states at near atomic resolution. We use the model to address two questions: (1) are bare F-actin modes of deformation conserved among the experimentally observed models and (2) do actin-binding proteins change F-actin's flexibility along one or more low modes of deformation? We find that the lowest mode shapes of the molecule are conserved across distinct F-actin models, as well as the bacterial homolog ParM, and that the actin-bundling protein fimbrin decreases significantly the torsional stiffness of F-actin while the cross-linking protein α-actinin does not. Because F-actin is itself highly conserved, these actin-binding proteins may provide a means to tune its stability and mechanical properties for specific cellular processes.