Stabilizing effect of amino acids on protein and colloidal dispersions

• 成果类型: Article
• 署名作者: Mao, Ting; Xu, Xufeng; Winkler, Pamina M.; Siri, Cecilia; Poliukhina, Ekaterina; Silva, Paulo Jacob; Xu, Nan; Hu, Yu; Al Zahabi, Karim; La Polla, Remi; Luo, Zhi; Ong, Quy; Alexander-Katz, Alfredo; Stellacci, Francesco
• 署名单位: Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Southern University of Science & Technology; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne
• 刊物名称: NATURE
• ISSN/ISSBN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-025-09506-w
• 发表日期: 2025-09-25
• 关键词: liquid-phase-separation; 2nd virial-coefficients; lysozyme solutions; stress; ultracentrifugation; aggregation; mechanisms; proline; water

摘要

Amino acids (AAs) have a long history of being used as stabilizers for biological media1. For example, they are important components in biomedical formulations. The effect of AAs on biological systems is also starting to be appreciated. For example, it is believed that water-stressed cells increase the levels of AAs to prevent protein aggregation2. Several hypotheses have been put forward regarding their function, ranging from water-structuring3 to hydrotropic4 to specific effects such as stabilization against misfolding, yet it is not known whether their stabilizing function is protein specific or a generic colloidal property. Here we deduce that AAs possess a new and broad colloidal property: they stabilize patchy nanoscale colloids by adsorbing onto their surfaces through weak interactions. We demonstrate this general property by careful experimental evaluation of the stabilizing effect of AAs on dispersions of various proteins, plasmid DNA and non-biological nanoparticles. Furthermore, we develop a theoretical framework that captures this phenomenon and experimentally corroborate several new broad theoretical implications that apply beyond AAs. In vivo experiments further demonstrate that the addition of 1 M proline to insulin doubles its bioavailability in blood. Overall, our results indicate that the role of small molecules is as important as that of ionic strength and should always be reported in biophysics experiments.