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| Home > Articles > Published articles > Citrate-Assisted Regulation of Protein Stability and Secretability from Synthetic Amyloids |
(Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia) (Institut de Recerca Sant Pau) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
| Date: | 2025 |
| Abstract: | 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. |
| Grants: | Agencia Estatal de Investigación PDC2022-133858-I00 Agencia Estatal de Investigación PID2019-105416RB-I00 Agencia Estatal de Investigación PID2022-1368450-OB-10 Instituto de Salud Carlos III PI20/00400 Instituto de Salud Carlos III PI23/00318 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00092 Ministerio de Sanidad y Consumo CB06/01/0014 Ministerio de Sanidad y Consumo CB06/01/1031 Instituto de Salud Carlos III CP19/00028 |
| Note: | Altres ajuts: acords transformatius de la UAB |
| Note: | Altres ajuts: JMS is supported with a María Zambrano postdoctoral researcher contract (677904) from Ministerio de Universidades and European Union ("Financed by European Union-Next GenerationEU") |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Recombinant proteins ; Biomaterials ; Protein secretion ; Endocrine-like function ; Cytotoxic proteins ; Degradation ; Materials ; Nanoparticles ; Peptides and proteins ; Toxicity |
| Published in: | ACS applied materials & interfaces, Vol. 17, Issue 10 (March 2025) , p. 14940-14951, ISSN 1944-8252 |
| Related work: | López-Laguna, Hèctor; T. P. Favaro, Marianna; VOLTÀ-DURÁN, ERIC; Parladé, Eloi; Sánchez, Julieta; Chellou-Bakkali, Sara; Corchero Nieto, José Luis; Unzueta, Ugutz; Villaverde, Antonio; Vazquez, Esther, 2024, "Replication data for Citrate-assisted regulation of protein stability and secretability from synthetic amyloids", CORA.Repositori de Dades de Recerca https://doi.org/10.34810/data1850 |
