Year: 2025
Type: article
Abstract: Biomolecular condensates are dynamic, membraneless compartments that emerge through phase separation of specific proteins and nucleic acids, regulating key biochemical processes within cells. Inspired by these natural systems, we recently developed a modular platform for engineering synthetic ribonucleic acid (RNA) condensates using a multistranded branched RNA motif, termed a nanostar. Here, we employ coarse-grained modeling and molecular dynamics (MD) simulations using the oxRNA2 platform to quantify conformational dynamics of 3-, 4-, and 5-arm nanostars. We define flexibility as the standard deviation of interarm angle distributions and geometry as the mean interarm angle. Across valencies at 37 °C and 0.15 M monovalent salts (NaCl), increasing the arm number reduces the mean angle as expected from geometry, while the dispersion of interarm angles remains comparable, indicating similar flexibility. Salt increases the mean angle in 4- and 5-arm nanostars and increases the temperature dependence of interarm angles. In contrast, the 3-arm nanostar is largely unaffected by salt and temperature over the studied ranges. Lastly, at 1.0 M salt and 37 °C, DNA nanostars adopt larger mean angles compared to RNA nanostars across all valencies, suggesting that backbone chemistry shifts preferred geometry more than it broadens fluctuations. These results illuminate how valency, salt, and temperature differentially control geometry versus flexibility, informing the design of synthetic RNA nanostars and thus condensates with predictable material responses.
Source: Chem & Bio Engineering
DOI: 10.1021/cbe.5c00093
Authors: Pradnya R. Kadam, Justine Lim, Mahdi Dizani, Jaimie Marie Stewart
Institution: University of California, Los Angeles
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Funder: Alfred P. Sloan Foundation
OpenAlex ID: W4415796256