A first order phase transition mechanism underlies protein aggregation in mammalian cells
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elife-39695-v1.pdf
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Author(s)
Meriin, Anatoli
Sherman, Michael Y
Narayanan, Arjun
Andrews, James Owen
Spille, Jan Hendrik
Cisse, Ibrahim I
Date Issued
February 2019
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Narayanan, Arjun et al. “A First Order Phase Transition Mechanism Underlies Protein Aggregation in Mammalian Cells.” eLife 8 (February 2019): e39695 © 2019 The Authors
Version
Final published version
Abstract
The formation of misfolded protein aggregates is a hallmark of neurodegenerative diseases. The aggregate formation process exhibits an initial lag phase when precursor clusters spontaneously assemble. However, most experimental assays are blind to this lag phase. We develop a quantitative assay based on super-resolution imaging in fixed cells and light sheet imaging of living cells to study the early steps of aggregation in mammalian cells. We find that even under normal growth conditions mammalian cells have precursor clusters. The cluster size distribution is precisely that expected for a so-called super-saturated system in first order phase transition. This means there exists a nucleation barrier, and a critical size above which clusters grow and mature. Homeostasis is maintained through a Szilard model entailing the preferential clearance of super-critical clusters. We uncover a role for a putative chaperone (RuvBL) in this disassembly of large clusters. The results indicate early aggregates behave like condensates. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
MIT Department
Massachusetts Institute of Technology. Center for Materials Science and Engineering
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.7554/eLife.39695
