Conclusion
In summary, we have demonstrated how artificial molecular chaperones can
serve opposite roles, i.e. catalyst or inhibitor, depending on their
dosage in regulating the assembly of peptides. Low dosages of molecular
chaperones catalyze peptide assembly into fibrils through multi-step
phase separation, while high dosages trap peptides into coacervate
intermediates and therefore inhibit assembly. This study provides a clue
to elucidate the intricate relationship between phase separation and
peptide assembly. When a phase separated system contains multiple
components, additives, or impurities, careful examination of their
dosage effects on assembly kinetics should not be overlooked. Moreover,
this study provides insights into the multifaceted roles chaperones may
play in regulating molecular assembly, facilitates the development of
chaperone-assisted assembly strategy [24, 42, 43,
52-55] for the construction of complex assembly systems.
Materials and Methods
Detailed materials and methods are included in SI Appendix . The
fibrillation of peptides was characterized by TEM, CLSM, ThT
fluorescence, and CD. Interactions between CMD and peptides were studied
by FRET, SPR, and ITC.
Acknowledgements
We thank Junjie Chen (Core Facility of Biomedical Sciences, Xiamen
University, Xiamen 361001, PR China) for helpful discussion and
assistance in the experiments. This work was supported by the National
Natural Science Foundation of China (NSFC) (Nos. 21991130, 21991131,
21971216, 21971217, 22372139, 22250004), the Top-Notch Young Talents
Program of China, and the Fundamental Research Funds for the Central
Universities of China (No. 20720210007).
Conflict of Interests
The authors declare no competing interests.