Contagious Aggregation: Transmittable Protein Aggregation in Cellular Communities Initiated by Synthetic Cells

Abstract

Aggregation of amyloidogenic proteins causingneurodegenerative diseases is an uncontrollable and contagiousprocess that is often associated with lipid membranes in a highlycomplex physiological environment. Although several approachesusing natural cells and membrane models have been reported,systematic investigations focusing on the association with themembranes are highly challenging, mostly because of the lack ofproper molecular tools. Here, we report a new supramolecularapproach using a synthetic cell system capable of controlling theinitiation of protein aggregation and mimicking various conditions of lipid membranes, thereby enabling systematic investigations ofmembrane-dependent effects on protein aggregation by visualization. Extending this strategy through concurrent use of syntheticcells and natural cells, we demonstrate the potential of this approach for systematic and in-depth studies on interrogating inter- andintracellularly transmittable protein aggregation. Thus, this new approach offers opportunities for gaining insights into thepathological implications of contagious protein aggregation associated with membranes for neurotoxicity.