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

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Protein Engineering

Background:

• Hexahistidine-tagged proteins self-assemble into dynamic depots using divalent cations.
• These protein depots show potential as sustained drug delivery systems.
• Understanding component influence on depot disintegration and release is crucial.

Purpose of the Study:

• To investigate how protein properties and cation choice affect the disintegration and secretory performance of protein depots.
• To identify key protein characteristics governing release kinetics and total releasable protein fraction.
• To provide insights for engineering efficient and tailored secretory granules for biological applications.

Main Methods:

• Utilized four distinct model proteins and four different cation formulations.
• Controlled protein aggregation to form microscale depots.
• Analyzed the impact of protein properties and cations on release kinetics and disintegration.

Main Results:

• Cation choice had a moderate influence, while protein properties significantly impacted release.
• Electrostatic charge at the amino terminus, instability, and hydropathicity indexes were key determinants of depot disintegration.
• Identified specific protein characteristics that control the release profile and fraction of releasable protein.

Conclusions:

• Protein properties are critical for controlling the disintegration and release kinetics of hexahistidine-tagged protein depots.
• Tailoring protein characteristics enables the fabrication of efficient, biocompatible, and homogenous secretory granules.
• These findings facilitate the development of customized drug delivery platforms for biological systems.