Structural Reorganization of Parallel Actin Bundles by Crosslinking Proteins: Incommensurate States of Twist

TL;DR

This study models how crosslinking proteins induce overtwisting in parallel actin bundles, revealing a sensitive phase transition influenced by linker flexibility and predicting diverse intermediate structures.

Contribution

It introduces a coarse-grained model linking crosslinker properties to actin bundle twist states and thermodynamic transitions, highlighting the impact of linker flexibility on bundle structure.

Findings

Flexible crosslinkers cause smooth twist distortions.

Rigid crosslinkers induce sharp phase transitions.

Intermediate structures with alternating untwisted and overtwisted domains.

Abstract

We construct a coarse-grained model of parallel actin bundles crosslinked by compact, globular bundling proteins, such as fascin and espin, necessary components of filapodial and mechanosensory bundles. Consistent with structural observations of bundles, we find that the optimal geometry for crosslinking is overtwisted, requiring a coherent structural change of the helical geometry of the filaments. We study the linker-dependent thermodynamic transition of bundled actin filaments from their native state to the overtwisted state and map out the "twist-state'' phase diagram in terms of the availability as well as the flexibility of crosslinker proteins. We predict that the transition from the uncrosslinked to fully-crosslinked state is highly sensitive to linker flexibility: flexible crosslinking smoothly distorts the twist-state of bundled filaments, while rigidly crosslinked bundles undergo a phase transition, rapidly overtwisting filaments over a narrow range of free crosslinker concentrations. Additionally, we predict a rich spectrum of intermediate structures, composed of alternating domains of sparsely-bound (untwisted) and strongly-bound (overtwisted) filaments. This model reveals that subtle differences in crosslinking agents themselves modify not only the detailed structure of parallel actin bundles, but also the thermodynamic pathway by which they form.