Engineering the Liquid‐to‐Solid Transition of Biomolecular Condensates: Molecular Mechanisms, Control Strategies, and Applications
Source abstract
Abstract
ABSTRACT Biomolecular condensates are formed through liquid–liquid phase separation (LLPS). They are highly dynamic, membraneless compartments within cells. The liquid‐to‐solid transition (LST) of these condensates plays a central role in regulating cellular physiological functions, maintaining tissue structural stability, and driving disease progression. Engineering LST has emerged as a major research frontier, integrating biophysics, synthetic biology, and materials science. This review systematically outlines the molecular grammar governing LST, key engineering strategies for its spatiotemporal control, and emerging applications in designed biological systems. We further discuss current challenges and future directions for harnessing LST as a design principle in systems chemistry and synthetic biology.
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Research context
OpenAlex topics: RNA Research and Splicing · Nuclear Structure and Function · Plant Molecular Biology Research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Earth‐Life Science Institute Institute of Science Tokyo Tokyo Japan
Department of Ultrasound Women's Hospital School of Medicine Zhejiang University Hangzhou China
MediCity Research Laboratory University of Turku Turku Finland
Key Laboratory of Biomedical Engineering of Ministry of Education Department of Biomedical Engineering Zhejiang University Hangzhou China
CNRS Centre de Recherche Paul Pascal Université De Bordeaux Pessac France
Department of Anesthesiology and Surgical Intensive Care Unit Xinhua Hospital School of Medicine and School of Biomedical Engineering Shanghai Jiao Tong University Shanghai China
State Key Laboratory of Oncogenes and Related Genes Institute For Personalized Medicine Shanghai Jiao Tong University Shanghai China
School of Life Science and Technology Northwestern Polytechnical University Xi'an Shaanxi China
Funding
Fundamental Research Funds for the Central Universities · Japan Society for the Promotion of Science
References (92)
Show source-provided references
1. 10.1038/s41589-022-01175-410.1038/s41589-022-01175-4 ↗
2. 10.1016/j.sbi.2023.10274210.1016/j.sbi.2023.102742 ↗
3. 10.1146/annurev-biophys-121219-08162910.1146/annurev-biophys-121219-081629 ↗
4. 10.1038/s41567-024-02558-110.1038/s41567-024-02558-1 ↗
5. 10.1016/j.bpj.2024.11.02010.1016/j.bpj.2024.11.020 ↗
6. 10.1103/PRXLife.2.02301110.1103/PRXLife.2.023011 ↗
7. 10.1021/acs.nanolett.3c0077310.1021/acs.nanolett.3c00773 ↗
8. 10.1360/TB-2024-115810.1360/TB-2024-1158 ↗
9. 10.1016/j.tibs.2020.12.00510.1016/j.tibs.2020.12.005 ↗
10. 10.1093/procel/pwad05710.1093/procel/pwad057 ↗
11. 10.1021/acs.jpcb.3c0142610.1021/acs.jpcb.3c01426 ↗
12. 10.1038/s41557-025-01762-710.1038/s41557-025-01762-7 ↗
13. 10.1021/acsami.4c1379210.1021/acsami.4c13792 ↗
14. 10.1101/2025.10.23.68405910.1101/2025.10.23.684059 ↗
15. 10.1021/acsnano.2c0841010.1021/acsnano.2c08410 ↗
16. 10.1038/s41557-024-01686-810.1038/s41557-024-01686-8 ↗
17. 10.1038/s41467-024-54510-910.1038/s41467-024-54510-9 ↗
18. 10.1038/s41565-024-01726-x10.1038/s41565-024-01726-x ↗
19. 10.1002/pro.516310.1002/pro.5163 ↗
20. 10.1021/jacs.3c0867410.1021/jacs.3c08674 ↗
21. 10.1016/j.bpj.2022.06.01310.1016/j.bpj.2022.06.013 ↗
22. 10.48550/arXiv.2407.2171010.48550/arXiv.2407.21710 ↗
23. 10.1371/journal.pcbi.100702810.1371/journal.pcbi.1007028 ↗
24. 10.1038/s41467-023-41274-x10.1038/s41467-023-41274-x ↗
25. 10.1073/pnas.221017711910.1073/pnas.2210177119 ↗
26. 10.1083/jcb.20210317510.1083/jcb.202103175 ↗
27. 10.1073/pnas.220224011910.1073/pnas.2202240119 ↗
28. 10.1016/j.bpj.2024.12.01710.1016/j.bpj.2024.12.017 ↗
29. 10.1021/jacs.5c0734010.1021/jacs.5c07340 ↗
30. 10.1039/D0CS00307G10.1039/D0CS00307G ↗
31. 10.1021/acs.biomac.4c0022410.1021/acs.biomac.4c00224 ↗
32. 10.1016/j.chempr.2023.05.00910.1016/j.chempr.2023.05.009 ↗
33. 10.1002/smll.20240166510.1002/smll.202401665 ↗
34. 10.1021/jacs.5c0905010.1021/jacs.5c09050 ↗
35. 10.1002/advs.20251831210.1002/advs.202518312 ↗
36. 10.1063/5.024422710.1063/5.0244227 ↗
37. 10.1021/acs.jpclett.5c0026210.1021/acs.jpclett.5c00262 ↗
38. 10.1039/D5MA01006C10.1039/D5MA01006C ↗
39. 10.3390/v1210117910.3390/v12101179 ↗
40. 10.1155/2022/716538710.1155/2022/7165387 ↗
41. 10.1186/s13024-020-00414-310.1186/s13024-020-00414-3 ↗
42. 10.1016/j.arr.2023.10207710.1016/j.arr.2023.102077 ↗
43. 10.1126/sciadv.adi734710.1126/sciadv.adi7347 ↗
44. 10.7554/eLife.100284.310.7554/eLife.100284.3 ↗
45. 10.1016/j.jmb.2020.16679410.1016/j.jmb.2020.166794 ↗
46. 10.1093/nar/gkac86610.1093/nar/gkac866 ↗
47. 10.1126/science.aaf684610.1126/science.aaf6846 ↗
48. 10.1021/jacs.5c0729510.1021/jacs.5c07295 ↗
49. 10.1002/anie.20170319110.1002/anie.201703191 ↗
50. 10.1039/D4SM01477D10.1039/D4SM01477D ↗
51. 10.1038/s41467-023-44278-910.1038/s41467-023-44278-9 ↗
52. 10.1021/jacs.4c0403610.1021/jacs.4c04036 ↗
53. 10.1002/smtd.20230176010.1002/smtd.202301760 ↗
54. 10.1021/acsami.3c0072710.1021/acsami.3c00727 ↗
55. 10.1021/acs.jpclett.4c0046010.1021/acs.jpclett.4c00460 ↗
56. 10.1038/s41467-022-35001-110.1038/s41467-022-35001-1 ↗
57. 10.1039/C9QM00598F10.1039/C9QM00598F ↗
58. 10.1016/j.cell.2016.11.05410.1016/j.cell.2016.11.054 ↗
59. 10.1007/978‐1‐0716‐3401‐1_1710.1007/978‐1‐0716‐3401‐1_17 ↗
60. 10.1002/smtd.20230172410.1002/smtd.202301724 ↗
61. 10.1038/s41477-020-00800-110.1038/s41477-020-00800-1 ↗
62. 10.1126/sciadv.abd356810.1126/sciadv.abd3568 ↗
63. 10.1016/j.mser.2023.10076210.1016/j.mser.2023.100762 ↗
64. 10.1126/science.adk906710.1126/science.adk9067 ↗
65. 10.1002/adma.20241470310.1002/adma.202414703 ↗
66. 10.1002/adma.20180817910.1002/adma.201808179 ↗
67. 10.1002/ange.20210215810.1002/ange.202102158 ↗
68. 10.3390/molecules2903068110.3390/molecules29030681 ↗
69. 10.1126/sciadv.aax315510.1126/sciadv.aax3155 ↗
70. 10.1002/anie.20210006410.1002/anie.202100064 ↗
71. 10.1016/j.actbio.2024.05.02410.1016/j.actbio.2024.05.024 ↗
72. 10.1038/s41563-018-0182-610.1038/s41563-018-0182-6 ↗
73. 10.1021/jacs.4c1788010.1021/jacs.4c17880 ↗
74. 10.1038/s41467-023-36331-410.1038/s41467-023-36331-4 ↗
75. 10.1038/s41565-020-0731-410.1038/s41565-020-0731-4 ↗
76. 10.1021/acsami.5c0624810.1021/acsami.5c06248 ↗
77. 10.1021/jacs.4c0668810.1021/jacs.4c06688 ↗
78. 10.1016/j.tibtech.2025.02.01210.1016/j.tibtech.2025.02.012 ↗
79. 10.1038/s41467-025-59118-110.1038/s41467-025-59118-1 ↗
80. 10.1016/j.cell.2015.07.04710.1016/j.cell.2015.07.047 ↗
81. 10.1021/jacs.5c0136910.1021/jacs.5c01369 ↗
82. 10.1038/s41586-021-03703-z10.1038/s41586-021-03703-z ↗
83. 10.1007/s11427-024-2661-310.1007/s11427-024-2661-3 ↗
84. 10.1038/s41580-025-00897-210.1038/s41580-025-00897-2 ↗
85. 10.1038/s41589-022-01204-210.1038/s41589-022-01204-2 ↗
86. 10.1073/pnas.241950712210.1073/pnas.2419507122 ↗
87. 10.1016/j.bpj.2023.07.01310.1016/j.bpj.2023.07.013 ↗
88. 10.1038/s41557-024-01706-710.1038/s41557-024-01706-7 ↗
89. 10.1038/s44222-025-00349-810.1038/s44222-025-00349-8 ↗
90. 10.1021/acsnano.5c1473110.1021/acsnano.5c14731 ↗
91. 10.1016/j.jmb.2025.16936410.1016/j.jmb.2025.169364 ↗
92. 10.1038/s41467-025-57772-z10.1038/s41467-025-57772-z ↗