Authoritative review: actin polymerization rate constants, profilin/thymosin-β4 monomer pool, Arp2/3 + formin nucleation, cofilin severing, capping. Backbone reference for any STRC actin compute.
Citation
Pollard TD. “Actin and Actin-Binding Proteins.” Cold Spring Harbor Perspectives in Biology, 8: a018226, 2016. doi:10.1101/cshperspect.a018226. PMC4968159. PMID 26988969. Re-ingested from MinerU output 2026-04-25.
TL;DR
Comprehensive review of actin biochemistry and the regulatory protein families (profilin, thymosin-β4, cofilin, Arp2/3, formins, Ena/VASP, capping protein, tropomodulin, gelsolin, cross-linkers, tropomyosin). Establishes the canonical rate constants for monomer-, dimer-, trimer-, and end-specific reactions plus the geometric facts about the actin filament. Single highest-leverage reference for any STRC compute that touches actin assembly, stereocilia treadmilling, or WH2-driven nucleation.
Numbers that matter
Page numbers below refer to the MinerU-converted markdown at ~/BookLibrary/mineru-output/pollard2016/pollard2016/auto/pollard2016.md. Verbatim values from Pollard’s text; secondary citations preserved.
Actin monomer geometry & sequence
Parameter
Value
Source (PDF page)
Notes
Actin polypeptide length
375 residues
p.1 (§3)
Eukaryotic actin
Subunit half-stagger in filament
2.7 nm
p.1 (§3)
Two-strand right-handed helix
Filament short-pitch helix twist
167° per subunit
p.1 (§3)
Free filament
Subdomain organization
4 subdomains, ATP in cleft
p.1 (§3)
Strong contacts to subdomains 3, 4
Arp ↔ actin sequence identity
17–52 %
p.1 (§2)
Arp1–Arp11
Nucleotide binding (ATP/ADP) on monomeric actin
Reaction
k_on
k_off
K_d
Source
ATP binding to nucleotide-free monomer
6 µM⁻¹ s⁻¹
~10⁻² s⁻¹
nanomolar range
p.1 (§4) — De La Cruz & Pollard 1995
Effect of free divalent cation chelation on ATP k_off
—
↑ 20-fold
—
p.1 (§4)
Nucleation kinetics (spontaneous)
Step
Rate / property
Source
Dimer dissociation rate
~10⁶ s⁻¹
p.2 (§4) — Cooper 1983; Frieden 1983
Trimer subunit dissociation rate
~100 s⁻¹
p.2 (§4) — Cooper 1983; Frieden 1983
Stable nucleus
tetramer (full intermolecular contacts)
p.2 (§4)
Filament-end elongation (per Fig. 2 / §4)
End
Nucleotide
k_on (µM⁻¹ s⁻¹)
k_off (s⁻¹)
Critical conc.
Source
Barbed
ATP-actin
~10 (diffusion-limited)
~1
~0.1 µM
p.2 (§4) — Pollard 1986
Pointed
ATP-actin
much slower than barbed
—
—
p.2 (§4)
Both ends
Mg-ADP-actin
—
—
1.8 µM (same at both ends)
p.2 (§4) — Pollard 1986
ATP hydrolysis on the filament
Quantity
Value
Source
Mg-ATP hydrolysis rate on monomer
7 × 10⁻⁶ s⁻¹
p.2 (§4) — Blanchoin & Pollard 2002
Mg-ATP hydrolysis rate on filament subunit
0.3 s⁻¹
p.2 (§4) — Blanchoin & Pollard 2002
γ-Pi dissociation half-time from polymerized actin
~6 min
p.2 (§4) — Carlier & Pantaloni 1986
γ-Pi dissociation rate constant
~0.003 s⁻¹
p.2 (§4) — Carlier & Pantaloni 1986
Pi binding k_on (to ADP-actin filament)
~2 M⁻¹ s⁻¹
p.2 (§4) — Carlier & Pantaloni 1986
Pi K_d for polymerized ADP-actin
~1 mM (pH-dependent)
p.2 (§4)
Cellular actin pools
Quantity
Value
Source
Total actin in cells
50–200 µM
p.2 (§5)
Unpolymerized fraction
~50 % (25–100 µM range)
p.2 (§5)
Treadmilling rate at steady state
< 1 subunit/sec
p.2 (§4) — Wegner 1976
Profilin (p.2 §6)
Parameter
Value
Source
Profilin molecular weight
~13–14 kDa
p.2 (§6)
Profilin K_d for ATP-actin monomer
0.1 µM
p.2 (§6)
Profilin cellular concentration
50–100 µM
p.2 (§6)
Profilin K_d at barbed end (ATP-actin filament)
> 20 µM (weak)
p.2 (§6) — Courtemanche & Pollard 2013
Profilin function on barbed end
does not block elongation; can slow at high [profilin]
p.2 (§6)
Profilin secondary function
catalyzes ADP→ATP exchange on monomer
p.2 (§6) — Mockrin & Korn 1980
Thymosin-β4 (p.2 §6)
Parameter
Value
Source
Length
43 residues
p.2 (§6)
Architecture
N-terminal helix in barbed-end groove + C-terminal helix at pointed-end cleft
p.2 (§6) Fig. 5B
Cellular concentration
> 100 µM (leukocytes, platelets)
p.2 (§6)
K_d for Mg-ATP-actin
~1 µM (micromolar)
p.2 (§6)
Function
sequesters monomer; sterically blocks all polymerization-relevant interactions
p.2 (§6)
Cofilin & severing (§7)
Parameter
Value
Source
Cofilin molecular weight
~15 kDa
p.2 (§7)
Affinity rank for filament subunits
ADP > ADP-Pi ≈ ATP
p.3 (§7) — Cao 2006
Filament short-pitch twist when cofilin-decorated
162° (vs 167° free)
p.3 (§7) — McCullough 2011
Long-pitch helix repeat when cofilin-decorated
27 nm (vs 36 nm free)
p.3 (§7) — McCullough 2011
Severing optimum
sub-stoichiometric (interfaces between bare/decorated segments)
binds N-termini of two tropomyosin molecules → strengthens cap
p.4 (§10)
Function
blocks both addition AND loss; allows slow exchange in vivo
p.4 (§10)
Cross-linker ABDs (§11)
Parameter
Value
Source
Typical ABD K_d for F-actin
~10 µM
p.5 (§11)
Exchange timescale
sub-second
p.5 (§11)
Mechanical consequence
networks stiff under fast deformation, deformable on tens-of-seconds timescale
p.5 (§11) — Yao 2011; Xu 1998
Why this matters for STRC
h09 hydrogel — every parameter the WH2-bundling models use about actin (free monomer concentration, profilin/Tβ4 partitioning, treadmilling rate, ABD-class F-actin K_d as proxy) is in this one review. The note [[Recipe — Profilin Thymosin-β4 Monomer Pool Partitioning]] extracts the partitioning algorithm from §6.
Stereocilia mechanics — tropomodulin at the pointed end of stereocilia thin filaments is exactly the §10 tropomodulin mechanism. Capping protein 30-min off-rate (§10) is the right timescale to compare against bundle turnover.
Treadmilling — pointed-end vs barbed-end critical-concentration asymmetry (§4 + §10 Fig. 8) explains why stereocilia rootlets at the base disassemble while tips grow.
Cofilin filament geometry change (167°→162°, 36→27 nm) is not just a chemistry detail — it’s a mechanical-state change that any AFM/FEM model of stereocilia under cofilin regulation must account for. See [[Cofilin Filament Twist Geometry Change]].
Arp2/3 needs TWO NPFs — relevant if any STRC delivery strategy invokes Arp2/3-driven branched-network seeding. Simple “one WASp” models are wrong.
Relevance to hydrogel model (legacy section, retained)
The “K_d ~10 µM for ABD-class cross-linkers” (§11) is the best available proxy for WH2 × F-actin side-binding in the absence of direct measurement. The model’s WH2_KD_FACTIN_M = 5 µM is therefore in the right ballpark as an optimistic estimate but has no primary measurement backing. A more conservative estimate would be 10–100 µM or higher. WH2 itself (§6) binds in the barbed-end groove of monomeric actin — the side-binding affinity is an extrapolation, not a direct Pollard 2016 measurement.