Gastric pH-induced liquid-liquid phase separation between lactoferrin and osteopontin protects against proteolysis and modulates intestinal uptake.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Gastric pH-induced liquid-liquid phase separation between lactoferrin and osteopontin protects against proteolysis and modulates intestinal uptake.
Συγγραφείς: Liu L; Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Diseases, Hangzhou, Zhejiang 310052, China. Electronic address: lanliu@zju.edu.cn., Lin C; Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Diseases, Hangzhou, Zhejiang 310052, China., Zheng M; College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China., Tu X; College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China., Yu Y; College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China., Song Z; Department of Nutrition, University of California, Davis, CA 95616, USA., Qi G; Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Diseases, Hangzhou, Zhejiang 310052, China., Li S; College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China., Yang M; College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China; Zhejiang Provincial Key Laboratory of Silk and Silk Protein New Materials, Institute of Applied Bioresource Research, Zhejiang University, Hangzhou, Zhejiang 310058, China., Lönnerdal B; Department of Nutrition, University of California, Davis, CA 95616, USA., Shuai Y; College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China; Zhejiang Provincial Key Laboratory of Silk and Silk Protein New Materials, Institute of Applied Bioresource Research, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: shuaiy@zju.edu.cn.
Πηγή: Food research international (Ottawa, Ont.) [Food Res Int] 2026 Jul 01; Vol. 235, pp. 119117. Date of Electronic Publication: 2026 Apr 14.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science Country of Publication: Canada NLM ID: 9210143 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7145 (Electronic) Linking ISSN: 09639969 NLM ISO Abbreviation: Food Res Int Subsets: MEDLINE
Imprint Name(s): Original Publication: Ottawa, Ontario, Canada : Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science, c1992-
Ιατρικοί όροι (MeSH): Lactoferrin*/metabolism , Lactoferrin*/chemistry , Osteopontin*/metabolism , Osteopontin*/chemistry , Proteolysis* , Intestinal Absorption*, Hydrogen-Ion Concentration ; Animals ; Phase Separation ; Humans
Περίληψη: Harnessing heteroprotein interactions to control the gastrointestinal fate of bioactive milk proteins represents a promising strategy for improving infant nutrition and developing food formulations. Nonetheless, the influence of protein-protein interactions on the stability and digestibility remains largely unexplored. Here, we investigate the interaction between lactoferrin (LF) and osteopontin (OPN) and its impact on gastric stability and intestinal uptake. We demonstrate that LF and OPN undergo electrostatically driven liquid-liquid phase separation under mildly acidic conditions (pH ∼ 4), forming dense, spherical coacervates, while yielding only soluble complexes at neutral (pH ∼ 7) or irregular precipitates at extreme acidic conditions. This coacervation is tunable by environmental factors: physiological temperature (37°C) promotes droplet formation, whereas high ionic strength (50-100 mM) disrupts assembly. Importantly, in vivo studies demonstrate that LF-OPN coacervates formed at gastric pH confer substantial protection against proteolysis, resulting in 2.2-fold increased OPN uptake and 1.52-fold increased LF uptake in the jejunum compared to single-protein administration. These findings establish LF-OPN coacervation as a tunable, food-grade delivery system that leverages intrinsic protein interactions to enhance the oral bioavailability of bioactive proteins, offering a bio-inspired strategy for optimizing infant formula and functional foods.
(Copyright © 2026 Elsevier Ltd. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Bioavailability; Complex coacervation; Gastrointestinal digestion; Infant formula; Lactopontin; Oral delivery; pH-responsive assembly
Substance Nomenclature: EC 3.4.21.- (Lactoferrin)
106441-73-0 (Osteopontin)
Entry Date(s): Date Created: 20260505 Date Completed: 20260716 Latest Revision: 20260716
Update Code: 20260716
DOI: 10.1016/j.foodres.2026.119117
PMID: 42083182
Βάση Δεδομένων: MEDLINE