Protein features instruct the secretion dynamics from metal-supported synthetic amyloids

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 know...

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Detalles Bibliográficos
Autores: Parladé Molist, Eloi|||0000-0001-5750-550X, Sánchez Quiroga, Julieta María, Lopez Laguna, Hector, Unzueta, Ugutz, Villaverde Corrales, Antonio, Vazquez Gómez, Esther
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/408491
Acceso en línea:https://hdl.handle.net/2117/408491
https://dx.doi.org/10.1016/j.ijbiomac.2023.126164
Access Level:acceso abierto
Palabra clave:Particles
Drug delivery systems
Proteins
Recombinant proteins
Microparticles
Secretory amyloids
Drug delivery system
Time sustained drug release
Building blocks
Partícules (Matèria)
Medicaments -- Modes d'administració
Proteïnes
Àrees temàtiques de la UPC::Ciències de la salut
Descripción
Sumario: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.