A first-order phase transition underlies protein aggregation in mammalian cells

15 December 2015

Ibrahim Cissé
Department of Physics, MIT


Protein aggregation is ubiquitous in neuro-degeneration yet the in vivo formation and regulation mechanisms remain elusive. In this talk, we discuss how super-resolution imaging in fixed cells and light sheet imaging of living cells can help study the early steps of protein aggregation in mammalian cells, using misfolded protein aggregation associated with synuclein alpha interacting protein (synphilin). Analysis of cluster size distributions reveals the energetics of a steady-state super-saturated system undergoing a first order phase transition. We observed directly in living cells that individual condensates coarsen (large droplets grow while smaller droplets shrink), and coalesce (diffusing droplets merge upon contact) suggestive of a liquid condensed phase. This study describes a physical mechanism for protein aggregation and phase separation inside mammalian cells.

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