Protein features instruct the secretion dynamics from metal-supported synthetic amyloids
Por:
Parladé E., Sánchez J.M., López-Laguna H., Unzueta U., Villaverde A., Vázquez E.
Publicada:
1 ene 2023
Ahead of Print:
6 ago 2023
Resumen:
Hexahistidine-tagged proteins can be clustered by divalent cations into self-containing, dynamic protein depots at the microscale, which under physiological conditions leak functional protein. While such protein granules show promise in clinics as time-sustained drug delivery systems, little is known about how the nature of their components, that is, the protein and the particular cation used as cross-linker, impact on the disintegration of the material and on its secretory performance. By using four model proteins and four different cation formulations to control aggregation, we have here determined a moderate influence of the used cation and a potent impact of some protein properties on the release kinetics and on the final fraction of releasable protein. In particular, the electrostatic charge at the amino terminus and the instability and hydropathicity indexes determine the disintegration profile of the depot. These data offer clues for the fabrication of efficient and fully exploitable secretory granules that being biocompatible and chemically homogenous allow their tailored use as drug delivery platforms in biological systems.
Filiaciones:
Parladé E.:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Sánchez J.M.:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Departamento de Química, Cátedra de Química Biológica, Facultad de Ciencias Exactas, Físicas y Naturales, ICTA, Universidad Nacional de Córdoba, Av. Vélez Sársfield 1611, Córdoba, 5016, Argentina
Instituto de Investigaciones Biológicas y Tecnológicas (IIByT), CONICET-Universidad Nacional de Córdoba, Córdoba, 5016, Argentina
López-Laguna H.:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Unzueta U.:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, Barcelona, 08041, Spain
Josep Carreras Leukaemia Research Institute, Barcelona, 08025, Spain
Villaverde A.:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Vázquez E.:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain
hybrid, All Open Access; Hybrid Gold
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