Intracellular production of hydrogels and synthetic RNA granules by multivalent molecular interactions

Hideki Nakamura, Albert A. Lee, Ali Sobhi Afshar, Shigeki Watanabe, Elmer Rho, Shiva Razavi, Allister Suarez, Yu Chun Lin, Makoto Tanigawa, Brian Huang, Robert DeRose, Diana Bobb, William Hong, Sandra B. Gabelli, John Goutsias, Takanari Inoue

Research output: Contribution to journalArticlepeer-review

Abstract

Some protein components of intracellular non-membrane-bound entities, such as RNA granules, are known to form hydrogels in vitro. The physico-chemical properties and functional role of these intracellular hydrogels are difficult to study, primarily due to technical challenges in probing these materials in situ. Here, we present iPOLYMER, a strategy for a rapid induction of protein-based hydrogels inside living cells that explores the chemically inducible dimerization paradigm. Biochemical and biophysical characterizations aided by computational modelling show that the polymer network formed in the cytosol resembles a physiological hydrogel-like entity that acts as a size-dependent molecular sieve. We functionalize these polymers with RNA-binding motifs that sequester polyadenine-containing nucleotides to synthetically mimic RNA granules. These results show that iPOLYMER can be used to synthetically reconstitute the nucleation of biologically functional entities, including RNA granules in intact cells.

Original languageEnglish (US)
Pages (from-to)79-88
Number of pages10
JournalNature Materials
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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