RT Journal Article
SR Electronic
T1 A First Order Phase Transition Underlies the Formation of Sub-Diffractive Protein Aggregates in Mammalian Cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 148395
DO 10.1101/148395
A1 Arjun Narayanan
A1 Anatoli B. Meriin
A1 Michael Y. Sherman
A1 Ibrahim I. Cissé
YR 2017
UL http://biorxiv.org/content/early/2017/06/09/148395.abstract
AB Failure in protein quality control can often lead to protein aggregation, yet in neurodegenerative 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 in 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.