Specific Iron Binding to Natural Sphingomyelin Membrane Induced by Non-Specific Co-Solutes

TL;DR

This study reveals that iron ions selectively bind to sphingomyelin membranes under physiological conditions, disrupting membrane structure and potentially contributing to myelin sheath degradation in neurodegenerative diseases.

Contribution

It demonstrates for the first time that iron binds specifically to sphingomyelin membranes in salt-dependent, pH-sensitive manner, affecting membrane integrity.

Findings

Iron binds selectively to sphingomyelin membranes at physiological salt concentrations.

Iron binding disrupts membrane organization, potentially damaging myelin sheath.

Multivalent ions like La$^{3+}$ and Ca$^{2+}$ do not bind under similar conditions.

Abstract

Hypothesis: Sphingomyelin (SPM), a crucial phospholipid in the myelin sheath, is vital in insulating nerve fibers. We hypothesize that iron ions selectively bind to the phosphatidylcholine (PC) template within the SPM membrane under near-physiological conditions, disrupting membrane organization. These interactions could potentially contribute to the degradation of the myelin sheath, thereby playing a role in the development of neurodegenerative diseases. Experiments: We utilized synchrotron-based X-ray spectroscopy and diffraction techniques to study the interaction of iron ions with a bovine spinal cord SPM monolayer (ML) at the liquid-vapor interface under physiological conditions. The SPM ML serves as a model system, representing localized patches of lipids within a more complex membrane structure. The experiments assessed iron binding to the SPM membrane both in the presence of salts and with additional evaluation of the effects of various ion species on membrane behavior. Grazing incidence X-ray diffraction was employed to analyze the impact of iron binding on the structural integrity of the SPM membrane. Findings: Our results demonstrate that iron ions in dilute solution selectively bind to the PC template of the SPM membrane exclusively at near-physiological salt concentrations (e.g., NaCl, KCl, KI, or CaCl2) and are pH-dependent. In-significant binding was detected without these salts or at near-neutral pH with salts. The surface adsorption of iron ions is correlated with salt concentration, reaching saturation at physiological levels. In contrast, multivalent ions such as La$^{3+}$ and Ca2+ do not bind to SPM under similar conditions. Notably, iron binding to the SPM membrane disrupts its in-plane organization, suggesting that these interactions may compromise membrane integrity and contribute to myelin sheath damage associated with neurological disorders.