Citrate-Assisted Regulation of Protein Stability and Secretability from Synthetic Amyloids

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Název: Citrate-Assisted Regulation of Protein Stability and Secretability from Synthetic Amyloids
Autoři: Hèctor López-Laguna, Marianna T.P. Favaro, Sara Chellou-Bakkali, Eric Voltà-Durán, Eloi Parladé, Julieta Sánchez, José Luis Corchero, Ugutz Unzueta, Antonio Villaverde, Esther Vázquez
Zdroj: ACS Appl Mater Interfaces
UPCommons. Portal del coneixement obert de la UPC
Universitat Politècnica de Catalunya (UPC)
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
Informace o vydavateli: American Chemical Society (ACS), 2025.
Rok vydání: 2025
Témata: Recombinant proteins, Biomaterials, Endocrine-like function, Degradation, Toxicity, Àrees temàtiques de la UPC::Ciències de la salut, Nanoparticles, Cytotoxic proteins, Peptides and proteins, Protein secretion, Materials, Research Article
Popis: The mammalian endocrine system uses functional amyloids as dynamic depots to store and release protein hormones into the bloodstream. Such depots, acting as secretory granules within the microscale, are formed in specialized cells by the coordination between the ionic, divalent form of zinc (Zn2+) and the imidazole ring from accessible His residues. The reversibility of such cross-linking events allows for the release of monomeric or oligomeric forms of the functional protein for biological activity. In vitro, and mimicking such a natural coordination process, synthetic amyloidal granules with secretory properties can be fabricated using selected therapeutic proteins as building blocks. Then, these microparticles act as delivery systems for endocrine-like, sustained protein release, with proven applicability in vaccinology, cancer therapy, regenerative medicine, and as antimicrobial agents. While the temporal profile in which the protein is leaked from the material might be highly relevant to clinically oriented applications, the fine control of such parameters remains unclear. We have explored here how the kinetics of protein release can be regulated by intervening in the storage formulation of the granules, through the concentration of citrate not only as a buffer component and protein stabilizer but also as a chelating agent. The citrate-assisted, time-prolonged regulatable release of proteins, in their functional form, opens a spectrum of possibilities to adjust the preparation of synthetic secretory granules to specific clinical needs.
Druh dokumentu: Article
Other literature type
Popis souboru: application/pdf
Jazyk: English
ISSN: 1944-8252
1944-8244
DOI: 10.1021/acsami.4c20784
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/40009529
https://ddd.uab.cat/record/308730
Rights: CC BY
URL: http://creativecommons.org/licenses/by/4.0/This article is licensed under CC-BY 4.0
Přístupové číslo: edsair.doi.dedup.....e99f2429aad4bffbbd72c1de6a9b2f7d
Databáze: OpenAIRE
Popis
Abstrakt:The mammalian endocrine system uses functional amyloids as dynamic depots to store and release protein hormones into the bloodstream. Such depots, acting as secretory granules within the microscale, are formed in specialized cells by the coordination between the ionic, divalent form of zinc (Zn2+) and the imidazole ring from accessible His residues. The reversibility of such cross-linking events allows for the release of monomeric or oligomeric forms of the functional protein for biological activity. In vitro, and mimicking such a natural coordination process, synthetic amyloidal granules with secretory properties can be fabricated using selected therapeutic proteins as building blocks. Then, these microparticles act as delivery systems for endocrine-like, sustained protein release, with proven applicability in vaccinology, cancer therapy, regenerative medicine, and as antimicrobial agents. While the temporal profile in which the protein is leaked from the material might be highly relevant to clinically oriented applications, the fine control of such parameters remains unclear. We have explored here how the kinetics of protein release can be regulated by intervening in the storage formulation of the granules, through the concentration of citrate not only as a buffer component and protein stabilizer but also as a chelating agent. The citrate-assisted, time-prolonged regulatable release of proteins, in their functional form, opens a spectrum of possibilities to adjust the preparation of synthetic secretory granules to specific clinical needs.
ISSN:19448252
19448244
DOI:10.1021/acsami.4c20784