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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60345-9 |
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| author | Zhitao Liao Bowen Jia Dongshi Guan Xudong Chen Mingjie Zhang Penger Tong |
| author_facet | Zhitao Liao Bowen Jia Dongshi Guan Xudong Chen Mingjie Zhang Penger Tong |
| author_sort | Zhitao Liao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0ed99c6ed1cd4a76abf0acdadbf71b69 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0ed99c6ed1cd4a76abf0acdadbf71b692025-08-20T02:30:42ZengNature PortfolioNature Communications2041-17232025-06-0116111410.1038/s41467-025-60345-9Emergent mechanics of a networked multivalent protein condensateZhitao Liao0Bowen Jia1Dongshi Guan2Xudong Chen3Mingjie Zhang4Penger Tong5Department of Physics, Hong Kong University of Science and Technology, Clear Water BayDivision of Life Science, Hong Kong University of Science and Technology, Clear Water BayState Key Laboratory of Nonlinear Mechanics, Institute of Mechanics, Chinese Academy of SciencesDivision of Life Science, Hong Kong University of Science and Technology, Clear Water BayDivision of Life Science, Hong Kong University of Science and Technology, Clear Water BayDepartment of Physics, Hong Kong University of Science and Technology, Clear Water BayAbstract 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.https://doi.org/10.1038/s41467-025-60345-9 |
| spellingShingle | Zhitao Liao Bowen Jia Dongshi Guan Xudong Chen Mingjie Zhang Penger Tong Emergent mechanics of a networked multivalent protein condensate Nature Communications |
| title | Emergent mechanics of a networked multivalent protein condensate |
| title_full | Emergent mechanics of a networked multivalent protein condensate |
| title_fullStr | Emergent mechanics of a networked multivalent protein condensate |
| title_full_unstemmed | Emergent mechanics of a networked multivalent protein condensate |
| title_short | Emergent mechanics of a networked multivalent protein condensate |
| title_sort | emergent mechanics of a networked multivalent protein condensate |
| url | https://doi.org/10.1038/s41467-025-60345-9 |
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