What they found
Proteomics of mouse perilymph vs CSF by LC-MS/MS. Identified 228+ proteins. Key finding for our purpose: perilymph is enriched in protease inhibitors, not active proteases.
Numbers that matter
| Parameter | Value | Notes |
|---|---|---|
| Serine protease inhibitors (serpins) | 27.8% of total perilymph protein | Largest single functional category |
| Perilymph protein vs CSF | ~2.8× more concentrated than CSF | Mouse |
| Active proteases identified | ~15% of protein content | Lower category than inhibitors |
Key insight for K_PROTEOLYSIS: Perilymph is protease-inhibitor-rich. The dominant serpins (serpin a1d, a1a, a1e) would strongly suppress serine protease-mediated degradation of an unprotected peptide. However:
- Cathepsin D was identified (lysosomal aspartyl protease — released during cell stress)
- No functional protease activity assays were performed
- No peptide half-life measured
The 30-min half-life for K_PROTEOLYSIS = 1.4/h in the model is conservative in the correct direction (perilymph is less proteolytic than serum) but the actual value for a 14 kDa peptide in perilymph is unmeasured. CSF stability data (extrinsic trypsin at 0.04 μM is fully inhibited by endogenous CSF inhibitors) suggests peptides may actually be stable for hours in perilymph.
Access
PMC open access: https://pmc.ncbi.nlm.nih.gov/articles/PMC2940114/
Supplementary materials
None noted.
Connections
[source]hydrogel_phase4e_cochlear_pkpd — K_PROTEOLYSIS justification; paper supports that perilymph is protease-inhibitor-rich, but does NOT give t½ for a 14 kDa peptide- STRC Hypothesis Ranking — h09 proteolytic stability in cochlea