1. Intracellular production of hydrogels and synthetic RNA granules by multivalent molecular interactions
- Author
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Brian Huang, Shiva Razavi, Albert A. Lee, Shigeki Watanabe, Robert DeRose, Allison Suarez, William Hong, Elmer Rho, Hideki Nakamura, Takanari Inoue, Sandra B. Gabelli, Diana Bobb, John Goutsias, Yu Chun Lin, Makoto Tanigawa, and Ali Sobhi Afshar
- Subjects
0301 basic medicine ,Polymers ,Biocompatible Materials ,macromolecular substances ,010402 general chemistry ,complex mixtures ,01 natural sciences ,Article ,03 medical and health sciences ,Chlorocebus aethiops ,Animals ,General Materials Science ,RNA metabolism ,Molecular interactions ,COS cells ,Extramural ,Chemistry ,Mechanical Engineering ,technology, industry, and agriculture ,RNA ,Hydrogels ,General Chemistry ,Condensed Matter Physics ,Biocompatible material ,Molecular biology ,0104 chemical sciences ,030104 developmental biology ,Mechanics of Materials ,COS Cells ,Self-healing hydrogels ,Biophysics ,Intracellular - Abstract
Non-membrane bound, hydrogel-like entities, such as RNA granules, nucleate essential cellular functions through their unique physico-chemical properties. However, these intracellular hydrogels have not been as extensively studied as their extracellular counterparts, primarily due to technical challenges in probing these materials in situ. Here, by taking advantage of a chemically inducible dimerization paradigm, we developed iPOLYMER, a strategy for rapid induction of protein-based hydrogels inside living cells. A series of biochemical and biophysical characterizations, in conjunction with computational modeling, revealed that the polymer network formed in the cytosol resembles a physiological hydrogel-like entity that behaves as a size-dependent molecular sieve. We studied several properties of the gel and functionalized it with RNA binding motifs that sequester polyadenine-containing nucleotides to synthetically mimic RNA granules. Therefore, we here demonstrate that iPOLYMER presents a unique and powerful approach to synthetically reconstitute hydrogel-like structures including RNA granules in intact cells.
- Published
- 2017
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