Amyloid fibrils are highly ordered protein or peptide fibrillar aggregates associated with both neurodegenerative diseases and functional use in nature. The extraordinary stability and tunable self-assembly of amyloid fibrils have been motivated as potential nanomaterials.

Prof. Sarah Perrett at Institute of Biophysics (IBP) of Chinese Academy of Sciences and Prof. Tuomas Knowles' group in the Chemistry Department at the University of Cambridge, collaboratively used microfluidic techniques to generate enzymatically active microgels that are stabilized by amyloid nanofibrils.

A microgel is a three-dimensional colloidal network of micron-scale size and has biomedical applications, such as drug delivery and microsensor biomaterials. To date, most microgels have been generated using synthetic molecules, with the polymerization reaction requiring non-biocompatible conditions or reagents, such as extreme pH, temperature, reactive chemicals or UV radiation. In contrast, microgels composed from naturally occurring polymers such as proteins or peptides are more biocompatible and biodegradable. Protein-based materials offer the additional advantage that novel functions can be directly incorporated via gene fusion producing a single chimeric polypeptide that will be self-assemble and display the desired activity.

The yeast prion protein, Ure2, has been explored previously as a nanoscaffold for displaying and immobilizing enzymes via genetic fusion (Zhou et al. & Perrett (2014) ChemCatChem 6, 1961-1968). In the current study, a chimera containing the prion domain of Ure2 fused to the enzyme alkaline phosphatase was used as the material for microgel formation. The ability of the chimeric protein to self-assemble under mild conditions enables the formation of catalytic microgels whilst maintaining the integrity of the encapsulated enzyme. The enzymatically-active microgel particles show robust material properties and their porous architecture allows diffusion in and out of reactants and products. In combination with microfluidic droplet trapping approaches, enzymatically-active microgels illustrate the potential of self-assembling materials for enzyme immobilization and recycling, and biological flow-chemistry. These design principles can be adopted to create other bioactive amyloid-based materials with diverse functions.

This study entitled “Enzymatically Active Microgels from Self-Assembling Protein Nanofibrils for Microflow Chemistry” was published online in ACS Nano.

The work was funded by the National Natural Science Foundation of China and the 973 Program of the Ministry of Science and Technology.

Figure: The Ure2 prion domain as a scaffold for enzyme immobilization and microgel formation. (Image by ZHOU et al. & Perrett (2014) ChemCatChem 6,1961-1968 and ZHOU et al. & Perrett (2015) ACS Nano)