Synergistic Effects of Iron in the Presence of Physiological Monovalent Cosolute on Myelin Basic Protein (MBP) Drive Modification in the Structure and Interfacial Behavior at the Air–Water Interface

Myelin basic protein (MBP), an intrinsically disordered protein responsible for membrane compaction in the central nervous system, exhibits a strong sensitivity to environmental ionic conditions. To elucidate how metal ions and ionic environments influence the MBP structure and interfacial behavior, Langmuir films of MBP were developed on a pure water subphase and on subphases modified with FeCl₃ (40 μM), KCl (100 mM), FeCl₃ + KCl (40 μM + 100 mM), and at a reduced subphase pH (≈ 4.0) without added ions. Films at the air-water interface were examined using surface pressure-area (Π-A) isotherms, the barrier oscillation method to determine dynamic viscoelasticity, and Brewster angle microscopy (BAM) to visualize in situ morphological evolution and corresponding film thickness. To validate BAM-derived thickness observations, all films were transferred onto solid substrates and characterized by using X-ray reflectivity and atomic force microscopy, enabling the extraction of detailed structural and height information. Results from these techniques clearly demonstrate that the unique ion-facilitated assembly of MBP at the air-water interface governs the variation in interfacial properties of the films. Notably, the coexistence of Fe³⁺, hydrolyzed Fe(III) species, and K⁺ ions produces a synergistic effect, as relatively more iron adsorption takes place in the presence of K⁺ ions, as evidenced from XPS analysis, thereby altering MBP assembly at the air-water interface under near-physiological concentration of KCl. These findings reveal how a specific ionic environment modulates the self-organization of MBP and may provide insights into myelin instability under ionic dysregulation.