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Study Design

Methods
UV-vis absorption, steady-state fluorescence, circular dichroism spectroscopy, 1H NMR, and TDDFT calculations
Herein, we unveil the interaction between bilirubin (BIL), a liver metabolite, and a milk protein, casein (CAS), through an integrated experimental-computational approach. Encapsulation of BIL within CAS protein micelles was characterized by using UV-vis absorption, steady-state fluorescence, and circular dichroism (CD) spectroscopy. CD analysis revealed conformational modulation of BIL upon encapsulation, accompanied by Förster resonance energy transfer (FRET) from CAS's tryptophans to BIL. 1H NMR measurements determined specific binding interactions of BIL functional groups involved in micellar interactions, correlating photophysical and electronic properties. The binding affinity of BIL in CAS micelles was found to be on the order of 104 M-1 with a spontaneous binding process (-24.56 kJ/mol) driven by entropy gains (467.17 J/mol). TDDFT calculations unveiled red shifts in BIL's absorption spectra caused by the protein environment. This integrated experimental-computational study provides novel insights into synergetic interactions and structural dynamics between BIL and CAS, shedding light on the influence of milk proteins on bilirubin's behavior.

Research Insights

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