Material properties of biomolecular condensates emerge from nanoscale dynamics

• 成果类型: Article
• 署名作者: Galvanetto, Nicola; Ivanovic, Milos T.; Grosso, Simone A. Del; Chowdhury, Aritra; Sottini, Andrea; Nettels, Daniel; Best, Robert B.; Schuler, Benjamin
• 署名单位: University of Zurich; University of Zurich; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12213
• DOI: 10.1073/pnas.2424135122
• 发表日期: 2025-06-10
• 关键词: liquid phase-separation; linear viscoelasticity; prothymosin-alpha; polymer physics; BEHAVIOR; rouse; simulations; dimensions; STABILITY; density

摘要

Biomolecular condensates form by phase separation of biological polymers and have important functions in the cell-functions that are inherently linked to their physical properties at different scales. A notable aspect of such membraneless organelles is that their viscoelastic properties can vary by orders of magnitude, but it has remained unclear how these pronounced differences are rooted in the nanoscale dynamics at the molecular level. Here, we investigate a series of condensates formed by complex coacervation of highly charged disordered proteins and polypeptides that span about two orders of magnitude in bulk viscosity. We find that their viscosity is highly correlated with protein translational diffusion and nano- to microsecond chain dynamics. Remarkably, analytical relations from polymer physics can predict condensate viscosity from diffusivity and chain dynamics, and vice versa, even for more hydrophobic disordered proteins and for synthetic polyelectrolytes, indicating a mechanistic link across several decades of length- and timescales. Atomistic simulations reveal that the observed differences in friction-a key quantity underlying these relations-reflect differences in interresidue contact lifetimes as a function of arginine content and salt concentration, leading to the vastly different dynamics among condensates. The rapid exchange of interresidue contacts we observe may be a general mechanism for preventing dynamic arrest in compartments densely packed with polyelectrolytes, such as the cell nucleus.