Cofilin Filament Twist Geometry Change

P0 data. When cofilin binds the side of an actin filament, both the helical twist and the long-pitch repeat change. This is a mechanical-state change that any model of cofilin-regulated actin (including stereocilia rootlet remodeling) must carry.

Verbatim values

ParameterFree filamentCofilin-decorated filamentΔ
Short-pitch twist per subunit167°162°−5°
Long-pitch helix repeat36 nm27 nm−25 %
Outer-domain rotation (subdomains 1+2)0° (reference)~30° from flattened conformation+30°
Result”even more skewed than monomers”

Source: [Pollard 2016, p.3 §7], summarizing Galkin 2011 PNAS and McCullough 2011 Biophys J.

Mechanism (per Galkin 2011, McCullough 2011)

  1. The cofilin domain anchors in the barbed-end groove of one actin subunit (same site as twinfilin’s cofilin domain — see Paavilainen 2008).
  2. A second cofilin contact reaches subdomain 2 of the next actin subunit along the long-pitch helix (toward the pointed end).
  3. To accommodate this contact without steric clash between successive subunits along the short-pitch helix, the inter-subunit twist relaxes from 167° to 162°.
  4. The compounding effect is a 25 % shortening of the long-pitch repeat (36 → 27 nm) and a more flexible filament.

Mechanical / functional consequence

  • Filaments saturated with cofilin are stable (uniform elastic modulus).
  • Filaments with partial cofilin decoration sever preferentially at the boundary between bare and decorated segments — because of the abrupt mechanical mismatch (Elam 2013; Ngo 2015).
  • This is why severing is substoichiometric-optimal — see [[Cofilin Severing Substoichiometric Optimum]].

Relevance to STRC

  • Stereocilia actin rootlets and shaft are continuously pruned at the base, where cofilin/ADF concentrations are higher [Drummond 2015, broader literature]. Any model that simulates rootlet thinning under ADF/cofilin must use the cofilin-decorated geometry, not the free-filament geometry.
  • For the bundle-stiffness decomposition [[Hair Bundle Stiffness Decomposition]], K_SP includes the bending modulus of the actin rootlet — which scales (roughly) with the persistence length of the filament. A 27-nm-repeat cofilin-decorated filament has lower persistence length than the 36-nm free filament; this is a specific quantitative input that should not be ignored.

Anti-fabrication notes

  • Pollard 2016 reports the geometry change but does not give a numerical persistence-length ratio. McCullough 2011 reports filaments are “more flexible”; for a specific persistence-length ratio, retrieve McCullough 2011 directly.
  • The “30° outer-domain rotation” is approximate (“~30°” verbatim).

Connections