TY - JOUR T1 - A First Order Phase Transition Underlies the Formation of Sub-Diffractive Protein Aggregates in Mammalian Cells JF - bioRxiv DO - 10.1101/148395 SP - 148395 AU - Arjun Narayanan AU - Anatoli B. Meriin AU - Michael Y. Sherman AU - Ibrahim I. Cissé Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/19/148395.abstract N2 - Failure in protein quality control can often lead to protein aggregation, yet in neuro-degenerative diseases, by the time aggregates can be seen, the cells have advanced well into the disease pathology. Here, we develop a quantitative imaging approach to study the protein aggregation process in living mammalian cells with unprecedented spatio-temporal resolution. We find that sub-diffractive precursor aggregates may form even in untreated cells, and their size distribution is exactly as predicted for a system undergoing a first order phase transition. Practically, this implies that as soon as aggregates reach a critical size (Rc = 162 ± 4 nm untreated cells), they will spontaneously grow into large inclusions. Our data suggest that a previously uncharacterized, RuvBL1 dependent mechanism clears aggregates above the critical size. Our study unveils the existence of sub-diffractive aggregates in living cells; and the strong agreement between cellular data and a nucleation theory, based on first order phase transition, provides insight into regulatory steps in the early stages of aggregate formation in vivo. ER -