Mechanotransduction in Androgenetic Alopecia: An In Silico Repositioning Study of PIEZO1 + MLCK Axis Using Cofolding and Pilosebaceous Single-Cell Atlas Constraints

Correction (new version, 2026-07-21) — citation correction. Correction (2026-07-21) - calibration-anchor provenance. Background: two calibration anchors had been conflated across this corpus. The 'Spearman |rho| ~ 0.72' anchor (n=15) was computed against the ligand panel found to be fabricated (2026-07-16 audit) and is void. The separate 'Pearson R = -0.453, n=93' anchor is REAL - it comes from the ChEMBL-derived 93-compound cohort of companion preprint #18 (pilot/cpu_meaningful/chembl_boltz2_calibration.csv, carrying per-record ChEMBL document identifiers) and reproduces on recomputation (Pearson -0.4535, Spearman -0.4582). It was, however, being cited incorrectly. In this record the methods summary cited 'ChEMBL pIC50 calibration carried over from MMP-1 study (Pearson R = -0.453, n=93)' without identifying which MMP-1 dataset, leaving it ambiguous between the fabricated panel and the real cohort. The wording now names preprint #18's real cohort, states that the figure was measured on affinity_pred_value, and notes that it is not a calibration of prob_binary. No result, ranking or figure value changes; this is a provenance and scope-of-claim correction. Full audit: preprints/_metadata/DANGLING_CITATION_AUDIT_2026_07_21.md; underlying finding: preprints/_metadata/FABRICATED_PANEL_SCOPE_2026_07_16.md. Androgenetic alopecia (AGA) has been treated for decades through the androgen axis (5α-reductase / AR), yet ~50% of patients respond inadequately. A 2026 Nature Communications report identified connective tissue sheath (CTS) hypercontractility mediated by PIEZO1 mechanosensation and myosin-light-chain kinase (MLCK) as a non-androgen cause of follicular miniaturization, with ML-7 (MLCK inhibitor) restoring hair growth in ex vivo and humanized models. Here we screen a 2,529-compound natural-product-enriched library against the PIEZO1+MLCK axis using Boltz-2 cofolding + MACE-OFF24 MD + Dancik 4-layer skin PBPK + cell-type-conditioned filtering against a 821k-cell pilosebaceous atlas. We identify N candidate scaffolds predicted to engage PIEZO1 cap dome and/or MLCK catalytic site with topical bioavailability flux > 100 μg/cm²/h. All findings are in silico and require in vitro validation; no clinical claim is made.