Stereocilia biomechanics — validated parameters
Source agent: Domain 3 (Sonnet 4.6), 2026-04-23. Consumer: hydrogel_phase1_self_assembly.py + h09/h26/h02 bundle-mechanics gates.
Parameter table
| Parameter | Literature value | Source | Conditions | Status | Used in |
|---|---|---|---|---|---|
| Mouse OHC bundle stiffness (apical, P13-15, +HTC) | 5.12 ± 0.46 pN/nm | dulon-2019-htc-bundle-mechanics (Sci Adv, FM-AFM) | Mouse apical | ✅ primary | h09 Phase 1 bundle gate |
Mouse OHC bundle stiffness (apical, P13-15, −HTC Strc/Tecta null) | 2.05 ± 0.15 pN/nm | dulon-2019-htc-bundle-mechanics | Mouse apical | ✅ primary | HTC knockout baseline |
| HTC contribution to bundle stiffness | 3.07 pN/nm (~60% of WT) | dulon-2019-htc-bundle-mechanics | Derived | ✅ primary | h09 therapeutic target |
| Rat OHC bundle stiffness (1 kHz, P7-10) | 2.5 pN/nm | 2019-tobin-elife-tiplink-stiffness-gradients (Tobin eLife) | Rat apical | ✅ primary | CF-dependent baseline |
| Rat OHC bundle stiffness (4 kHz, P7-10) | 8.6 pN/nm | 2019-tobin-elife-tiplink-stiffness-gradients | Rat | ✅ primary | mid-cochlea |
| IHC bundle stiffness (rat, 1-4 kHz) | 1.7 → 3.8 pN/nm | 2019-tobin-elife-tiplink-stiffness-gradients | Rat | ✅ primary | reference |
| Tip-link tension (rat OHC 1→4 kHz) | 5 → 34 pN | 2019-tobin-elife-tiplink-stiffness-gradients | Rat | ✅ primary | gating context |
| HTC links per mature bundle (mouse OHC) | ~19 | dulon-2019-htc-bundle-mechanics (derived from 20-stereocilium bundle) | Mouse | ⚠ derived | h09 HTC density |
| HTC per-link stiffness (derived) | ~0.16 pN/nm | 3.07 pN/nm aggregate / 19 links | calculation | ⚠ derived | alternative to 7.5 in model |
| Aggregate HTC stiffness (Kozlov model) | 20 pN/nm | Kozlov 2011 Nature PMC3150833 | Bullfrog sacculus, finite-element fit | ✅ primary (non-mammalian) | upper-bound reference |
| HTC developmental stiffness trajectory (P9→P15, +HTC) | 0.92 → 5.4 pN/nm | dulon-2019-htc-bundle-mechanics | Mouse | ✅ primary | — |
STRC × TMEM145 Kd — NOT MEASURED ANYWHERE
| Source | Finding |
|---|---|
| 2026-04-17-derstroff-tmem145-ohc-stereocilia (Neuron 2026) | Main text: CoIP, nanoSPD, AF3 ipTM 0.79. SI contains only Fig S11 (CoIP band quantification). NO SPR, NO BLI. |
| NatComms 2025 TMEM145 paper (Reimann lab, parallel group) | CoIP + pull-down only. NO biophysical Kd. |
| verpy-2011-strc-tm-morphology (J Comp Neurol) | Localization/developmental only. No stiffness, no binding data. |
Verdict: no published experimental Kd for STRC × TMEM145 exists. The model’s 10 nM claim in Phase 4h competition math is unsupported. AF3 ipTM is structural plausibility, not affinity.
Red flags in current h09 models
| Model constant | Value | Problem |
|---|---|---|
K_HTC_PN_PER_NM = 7.5 | cites “Tobin 2019” | Wrong citation. Tobin 2019 measures K_HB = K_GS + K_SP only, NO HTC term. Real per-link value is 0.16 pN/nm (Dulon derived); aggregate bullfrog model is 20 pN/nm (Kozlov). 7.5 is between but not directly from any paper. |
WT_BUNDLE_STIFFNESS_PN_PER_NM = 1400 | — | Wrong by 150–560×. Real values 2.5–8.6 pN/nm (Dulon/Tobin). Adult basal extrapolation might reach ~20–80 pN/nm. 1400 likely a unit error. Also: this constant is DEAD CODE — gate3_bundle_stiffness() doesn’t reference it. |
HTC_PER_STEREOCILIUM = 6 | — | Unverified. Dulon’s ~19 links for ~20 stereocilia suggests ~1 link per adjacent pair (2 per stereocilium counting both sides). “6” may count diagonal links to non-adjacent rows or use a different architectural interpretation. Tsuprun & Santi 2002 (J Histochem Cytochem) would resolve — not yet retrieved. |
HTC_SPACING_NM = 8.0 | — | Unclear what it means. Inter-stereocilium center-to-center spacing is 250–450 nm. 8 nm matches a single peptide span (the connector molecule), not inter-stereocilium gap. Model comment should clarify. |
STRC_NORMAL_OHC_M = 1 μM (Phase 4h) | — | No paper quantifies STRC copy number per OHC. Flag as estimated. |
Structural claim that IS backed
“≥60% bundle stiffness restoration claim for h09 is biologically coherent.” Dulon 2019 directly shows HTC removal causes ~60% bundle stiffness loss (5.12 → 2.05 pN/nm). A synthetic HTC-substitute that recovers 60% of 5.12 (≈3 pN/nm) would bring a null-STRC bundle from 2.05 → 5.05 pN/nm = essentially WT. This is the realistic therapeutic target, not the 1400 pN/nm straw figure.
Connections
[part-of]_hub (literature-params)[see-also]strc-tmem145-interactions[see-also]STRC Stereocilia Bundle Mechanics Model[applies]STRC Synthetic Peptide Hydrogel HTC[applies]STRC Engineered Homodimer Avidity