Stabilizing effect of amino acids on protein and colloidal dispersions

Ting Mao, Xufeng Xu, Pamina M. Winkler, Cécilia Siri, Ekaterina Poliukhina, Paulo Jacob Silva, Nan Xu, Yu Hu, Karim Al Zahabi, Rémi Polla, Zhi Luo (), Quy Ong (), Alfredo Alexander-Katz () and Francesco Stellacci ()
Additional contact information
Ting Mao: Ecole Polytechnique Fédérale de Lausanne
Xufeng Xu: Ecole Polytechnique Fédérale de Lausanne
Pamina M. Winkler: Ecole Polytechnique Fédérale de Lausanne
Cécilia Siri: Ecole Polytechnique Fédérale de Lausanne
Ekaterina Poliukhina: Ecole Polytechnique Fédérale de Lausanne
Paulo Jacob Silva: Ecole Polytechnique Fédérale de Lausanne
Nan Xu: Southern University of Science and Technology
Yu Hu: Southern University of Science and Technology
Karim Al Zahabi: Massachusetts Institute of Technology
Rémi Polla: Ecole Polytechnique Fédérale de Lausanne
Zhi Luo: Southern University of Science and Technology
Quy Ong: Ecole Polytechnique Fédérale de Lausanne
Alfredo Alexander-Katz: Massachusetts Institute of Technology
Francesco Stellacci: Ecole Polytechnique Fédérale de Lausanne

Nature, 2025, vol. 645, issue 8082, 915-921

Abstract: Abstract 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-025-09506-w Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:645:y:2025:i:8082:d:10.1038_s41586-025-09506-w

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-025-09506-w

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().