Invited review: Manufacturing Whey Protein Colloidal Particles via Liquid Antisolvent Precipitation Method: Particle...

The liquid antisolvent (LAS) precipitation, also referred to as desolvation, has emerged as a promising strategy to manufacturing whey protein particles (WPP) with tunable structures and functionalities. In contrast with conventional heat-induced protein aggregation, protein aggregation induced by LAS processing is driven by protein supersaturation generated by a rapid reduction in solvent quality upon mixing with an antisolvent under ambient conditions. This review consolidates current knowledge on the mechanisms of LAS induced protein-protein aggregation, LAS processing variables, physicochemical properties and functionalities of protein aggregates derived from LAS precipitation. The underlying mechanisms of LAS-induced protein denaturation and aggregation are discussed; the discussion covers multiscale phenomena ranging from macroscopic precipitation, to molecular-level interactions and conformational changes. Furthermore, antisolvent concentration, pH, ionic strength and other critical processing parameters are discussed for their impacts on aggregate particle size, morphology, and particle colloidal stability. Although functionality studies remain limited, existing evidence demonstrates that LAS-derived WPP exhibits promising functionality in emulsion stabilization and serves as efficient nanocarriers for encapsulating bioactive compounds. Future research is recommended to focus on elucidating the "structure-function" relationships of LAS-derived WPP. Systematic investigations of their physicochemical properties and functionalities in different model food structures remain scarce compared with extensively studied heat-induced protein particles. Lastly, the differences in driving forces governing protein unfolding and aggregation in LAS and thermal processes imply that WPP produced via these 2 different routes may possess distinct structural and functional characteristics. However, direct comparative studies remain largely absent. Addressing this critical knowledge gap will be essential for clarifying the unique advantages of LAS processing and for accelerating the rational design of WPP as customizable functional ingredients for diverse and higher-margin applications beyond foods such as nutraceuticals and pharmaceuticals. This will further increase the net economic value of whey protein.