Whey protein phospholipid concentrate at the interface of function and health: Heat-induced protein interactions, bioactivity, and choline delivery.

Milk is a nutrient-packed biological fluid essential for early development, with the milk fat globule membrane (MFGM) playing a fundamental role in cognitive, bone, immune, and gastrointestinal health. Driven by increasing demand for high-protein and sustainable ingredients, the dairy industry has focused on coproducts such as whey protein phospholipid concentrate (WPPC), a microfiltration-derived fraction enriched in MFGM proteins and polar lipids. WPPC contains elevated levels of caseins and whey proteins and is notably enriched in membrane-bound glycoproteins and phospholipids that contribute to its functional and nutritional value. Thermal processing, while critical for safety and shelf-life, induces remodeling of both protein and lipid components of the MFGM. Heat treatment promotes whey protein unfolding and aggregation, driving their association with the MFGM through covalent and noncovalent interactions, while concurrently remodeling MFGM lipid microdomains, altering phospholipid distribution, and increasing susceptibility to lipid and protein oxidation. These interfacial changes can modify MFGM protein accessibility, enzymatic activity, oxidative stability, and digestion-derived peptide release, ultimately influencing downstream isolation of native MFGM bioactives from WPPC and the performance of membrane- and solvent-based fractionation strategies. Emerging opportunities for WPPC as a functional delivery matrix for phospholipid-bound nutrients, including choline, are also discussed in the context of translational nutrition and next-generation dairy ingredient development.