Hydrogen bonding
Adheres to hydrophilic surfaces (mica, hydroxyapatite).
Technology
Mussel adhesion
engineered
for medicine
We re-engineer the molecular mechanics of byssal adhesion into a reproducible recombinant protein — DOPA chemistry, cassette design, and safety evaluation.
Scientific Foundation
Scientific basis of mussel adhesion
Marine mussels (Mytilus galloprovincialis) attach firmly to rocks even under turbulent seas. This adhesion is driven by mussel foot proteins (MFPs) found in the adhesive plaque at the tip of the byssus. Novelglue re-engineers this adhesion system for reproducible, recombinant production.
Mfp-1 — Protective coating (metal surface adhesion)
Mfp-2 — EGF-like domain, protein–protein interaction
Mfp-3 — Primer (~20 mol% DOPA)
Mfp-4 — Elasticity
Mfp-5 — Strongest adhesion (~30 mol% DOPA)
Mfp-6 — Antioxidant activity
DOPA Chemistry
DOPA chemistry
DOPA (3,4-dihydroxyphenylalanine) enables adhesion across wet interfaces via multiple interactions:
Metal coordination
Binds to metal oxide surfaces (Ti, stainless steel).
Hydrophobic interaction
Adheres to nonpolar surfaces (polystyrene).
Covalent bonding
Post-oxidation quinone reacts with amines/thiols via Michael addition.
Surface-force-apparatus measurements report an adhesion energy of W ≈ 3×10⁻⁴ J/m² for Mfp-3 on mica, enough to support ~100 g of force per plaque [*]. A broader mechanistic review is available in Waite 2017 [*].
Cassette Design
Cassette architecture and functional domains
Novelglue designs the FP2 region as a swappable cassette. By fusing functional domains such as EGF, growth factors or targeting peptides, a single platform derives many application-specific adhesives. When an EGF cassette is loaded, EGFR → PI3K/Akt, MEK/ERK signaling supports proliferation and apoptosis suppression; dependence on EGF-containing niche factors in human intestinal organoids is well established in Fujii et al. 2018 [*]. For Novelglue-specific cell adhesion / proliferation data, see Kawakami et al. 2025 [*].
back buffer 0%
FP121 83%
CellTak™ 89%
noncoated 1%
FP121 reaches CellTak™-level adhesion.
BSA 0.8×
CellTak™ 2.4×
EGF only 2.5×
FP121 4.7×
FP121 outperforms EGF-only and CellTak™.
Recombinant Expression
Recombinant expression
| System | Pros | Cons | Yield |
|---|---|---|---|
| E. coli | High yield, low cost, fast | No DOPA modification, aggregation | 1.0–1.7 g/L |
| Yeast | PTM possible | Low yield, long duration | Low |
| Mammalian | Full modification | Very low yield, high cost | Very low |
Novelgen combines E. coli expression with mushroom tyrosinase PTM (25°C, 6 h, with ascorbic acid) to achieve both high yield and functional DOPA residues.
Safety Evaluation
Preclinical safety
Novelglue follows a tiered preclinical path: materials characterization → in vitro biological tests → animal studies → GLP/GMP re-execution. The list below tracks our progress against ISO 10993 and OECD guidance. All items will be re-executed under GLP/GMP grade conditions at the PMDA submission stage.
In vitro biological safety
- ✓ CytotoxicityISO 10993-5
- ✓ Genotoxicity (Ames / micronucleus)ISO 10993-3
- ✓ Erythrocyte hemolysisISO 10993-4
- ✓ Endotoxin (post LPS-removal)
- ✓ Cell migration (scratch assay)BALB 3T3, 11.2 µg/mL
Scratch assay with BALB 3T3 cells demonstrated enhanced cell migration at 11.2 µg/mL (Kawakami et al. 2025 [*]).
In vivo (animal studies)
- ✓ Systemic toxicity (single / repeat dose)OECD GD 129, acute oral LD50 predictionGLP-grade data to follow within ~6 months.
- … SensitizationISO 10993-10 (guinea-pig maximization)
- ✓ IrritationISO 10993-10 (rabbit intracutaneous)
- ✓ Local reactionISO 10993-6 (implantation)
- … BiodegradationResidue & tissue reaction after implantationIf not degraded in 30 days → consider long-term / carcinogenicity studies.
IC50
1.08 ± 0.30 mg/mL
LD50 (estimated)
1.41 ± 0.146 g/kg
Scratch assay
11.2 µg/mL
✓ = completed / … = in progress / — = planned. All items will be re-executed under GLP/GMP grade at PMDA submission. Primary data: Kawakami et al. 2025 (Materials & Design) and related internal studies.
IP Portfolio
IP portfolio
Applications
- Japan patent application filed
- PCT international application filed
- National phase entries planned for US / EU / CN
Strategy
- Composition of matter (FP121 sequence)
- Method of use (cell culture / bone / DDS)
- Manufacturing (DOPA modification conditions)
- Formulation
引用文献 / References
- [1]
Kawakami, Y. et al. (2025) Development of the FP121 series: Hybrid proteins mimicking marine adhesive proteins with cell adhesion and proliferation activity , Materials & Design .
View on ScienceDirect →Novelglue (FP121 シリーズ) の基盤論文。細胞接着・増殖活性・スクラッチアッセイ等の一次データを含む。
- [2]
Waite, J. H. (2017) Mussel adhesion – essential footwork , Journal of Experimental Biology , 220 , pp. 517-530 .
DOI: 10.1242/jeb.134056イガイ足糸接着の分子メカニズム総説。
- [3]
Lee, H., Dellatore, S. M., Miller, W. M., Messersmith, P. B. (2007) Mussel-inspired surface chemistry for multifunctional coatings , Science , 318 , pp. 426-430 .
DOI: 10.1126/science.1147241DOPA / polydopamine による多機能コーティングの基礎的研究。
- [4]
Lin, Q., Gourdon, D., Sun, C., Holten-Andersen, N., Anderson, T. H., Waite, J. H., Israelachvili, J. N. (2007) Adhesion mechanisms of the mussel foot proteins mfp-1 and mfp-3 , PNAS , 104 , pp. 3782-3786 .
DOI: 10.1073/pnas.0607852104Mfp-3 の mica 表面接着エネルギーを SFA で直接測定した代表論文 (W ≈ 3×10⁻⁴ J/m²)。
- [5]
Hughes, C. S., Postovit, L. M., Lajoie, G. A. (2010) Matrigel: A complex protein mixture required for optimal growth of cell culture , Proteomics , 10 , pp. 1886-1890 .
DOI: 10.1002/pmic.200900758Matrigel の組成の不均一性とロット間変動を定量的に評価。
- [6]
Aisenbrey, E. A., Murphy, W. L. (2020) Synthetic alternatives to Matrigel , Nature Reviews Materials , 5 , pp. 539-551 .
DOI: 10.1038/s41578-020-0199-8Matrigel 代替としての合成・組換え基材の比較レビュー。
- [7]
Fujii, M. et al. (2018) Human intestinal organoids maintain self-renewal capacity and cellular diversity in niche-inspired culture condition , Cell Stem Cell , 23 , pp. 787-793.e6 .
DOI: 10.1016/j.stem.2018.11.016EGF を含むニッチ因子に依存したヒト腸オルガノイド維持条件を示した代表論文。