Emergent mechanics of a networked multivalent protein condensate

Abstract Multivalent proteins can form membraneless condensates in cells by liquid-liquid phase separation, and significant efforts have been made to study their biochemical properties. Here, we demonstrate the emergent mechanics of a functional multivalent condensate reconstituted with six postsyna...

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Bibliographic Details
Main Authors: Zhitao Liao, Bowen Jia, Dongshi Guan, Xudong Chen, Mingjie Zhang, Penger Tong
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60345-9
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Summary:Abstract Multivalent proteins can form membraneless condensates in cells by liquid-liquid phase separation, and significant efforts have been made to study their biochemical properties. Here, we demonstrate the emergent mechanics of a functional multivalent condensate reconstituted with six postsynaptic density proteins, using atomic-force-microscopy-based mesoscale rheology and quantitative fluorescence measurements. The measured relaxation modulus and protein mobility reveal that the majority (80%) of the proteins in the condensate are mobile and diffuse through a dynamically cross-linked network made of the remaining (20%) non-mobile scaffold proteins. This percolating structure gives rise to a two-mode mechanical relaxation with an initial exponential decay followed by a long-time power-law decay, which differs significantly from simple Maxwell fluids. The power-law rheology with an exponent α ≃ 0.5 is a hallmark of weak bonds’ binding/unbinding dynamics in the multivalent protein network. The concurrent molecular and mechanical profiling thus provides a reliable readout for characterizing the mechanical state of protein condensates and investigating their physiological functions and associations with diseases.
ISSN:2041-1723