Specific iron binding to natural sphingomyelin membrane induced by non-specific co-solutes in solutions

Sphingomyelin (SPM), a ceramide derived phospholipid with a phosphatidyl choline (PC) moiety, is abundant in the myelin sheath that with proteins forms an extended plasma membrane that is wrapped around nerve fibers. The myelin sheath provides electrical insulation to facilitate conduction between neuronal nodes. To achieve electrical insulation the SPM membrane has to be intact and damages to the myelin sheath has been implicated in a variety of brain diseases. Understanding the structural integrity of SPM in different salt solutions and its interactions with different ions would provide the basis for exploring the potential physiological pathways in the ion-associated neurodegenerative diseases. In this study, using spinal bovine SPM as a model system, we form and study a monomolecular layer (ML) at a physiological solution interface to determine the effect of various ions and their complexes on the PC-template formed by the SPM. Surface sensitive synchrotron X-ray diffraction and spectroscopic techniques demonstrate that only under salt (NaCl or KCl) concentration close to physiological conditions, dilute concentrations of iron [Fe(III)] complexes in solution spontaneously bind to the charge-neutral PC group and affect its structure. More importantly, we find that iron does not accumulate at the interface in the absence of co-salt species such as KCl, NaCl, KI, or CaCl₂. Other cations such as (La³⁺ or Ca²⁺), under similar conditions, do not accumulate at the interface indicating the nature of iron accumulation is unique and involves a special mechanism. The X-ray diffraction at grazing incidence, indicates in-plane deteriorated organization of the SPM in the monolayer upon iron binding. Our study implies that PC rich cell-plasma membranes are highly susceptible to the binding of iron complexes, even at minute concentrations. Such binding can propagate and alter membrane integrity and can be a factor that damages the myelin sheath.