THESIS
2022
1 online resource (xiii, 96 pages) : illustrations (chiefly color)
Abstract
Formation of membraneless organelles or biological condensates via phase separation
hugely expands cellular organelle repertoire. Biological condensates are dense and
viscoelastic soft matters instead of canonical dilute solutions. Unlike discoveries of numerous
different biological condensates to date, mechanistic understanding of biological condensates
remains scarce. In this study, we developed an adaptive single molecule imaging method that
allows simultaneous tracking of individual molecules and their motion trajectories in both
condensed and dilute phases of various biological condensates. The method enables
quantitative measurements of phase boundary, motion behavior and speed of molecules in
both condensed and dilute phases as well as the scale and speed of molecular exchanges...[
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Formation of membraneless organelles or biological condensates via phase separation
hugely expands cellular organelle repertoire. Biological condensates are dense and
viscoelastic soft matters instead of canonical dilute solutions. Unlike discoveries of numerous
different biological condensates to date, mechanistic understanding of biological condensates
remains scarce. In this study, we developed an adaptive single molecule imaging method that
allows simultaneous tracking of individual molecules and their motion trajectories in both
condensed and dilute phases of various biological condensates. The method enables
quantitative measurements of phase boundary, motion behavior and speed of molecules in
both condensed and dilute phases as well as the scale and speed of molecular exchanges
between the two phases. Surprisingly, molecules in the condensed phase do not undergo
uniform Brownian motion, but instead constantly switch between a confined state and a
random motion state. The confinement is consistent with formation of large molecular
networks (i.e., percolation) specifically in the condensed phase. Thus, molecules in biological
condensates behave distinctly different from those in dilute solutions. This finding is of
fundamental importance for understanding molecular mechanisms and cellular functions of
biological condensates in general.
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