The liquid-to-solid transition of FUS is promoted by the condensate surface

• DOI: 10.1073/pnas.2301366120
• Publication Date: 2023-08-07T19:11:27Z
• Authors: Yi Shen; Anqi Chen; Wenyun Wang; Yinan Shen; Francesco Simone ...; Stefano Aime; Zizhao Wang; Seema Qamar; Jorge R. Espinosa; Adiran Garaizar; Peter St George-H...; Rosana Collepardo...; David A. Weitz; Daniele Vigolo; Tuomas P. J. Knowles
• Keywords: Biomolecular Condensates; Microscopy, Confocal; biomolecular condensates; Humans; RNA-Binding Protein FUS; Biological Sciences; protein; Rheology; Protein Aggregation, Pathological; optics; 3. Good health

A wide range of macromolecules can undergo phase separation, forming biomolecular condensates in living cells. These membraneless organelles are typically highly dynamic, formed reversibly, and carry out essential functions biological systems. Crucially, however, a further liquid-to-solid transition the lead to irreversible pathological aggregation cellular dysfunction associated with onset development neurodegenerative diseases. Despite importance this proteins, mechanism by which it is initiated normally functional unknown. Here we show, measuring changes structure, dynamics, mechanics time space, that single-component FUS do not uniformly convert solid gel, but rather liquid gel phases coexist simultaneously within same condensate, resulting inhomogeneous structures. Furthermore, our results show originates at interface between condensate dilute continuous phase, once initiated, gelation process propagates toward center condensate. To probe such spatially rheology during aging, use combination established micropipette aspiration experiments together two optical techniques, spatial dynamic mapping reflective confocal speckle microscopy. reveal spatiotemporal dimension highlight as critical element driving protein aggregation.