Myelin is a membranous structure critically important for human health. Historically, it was believed that myelin remained largely unchanged in the adult brain. However, recent research has shown that myelin is remarkably dynamic, capable of adjusting axonal conduction velocity and playing a role in learning, memory, and recovery from injury, in response to both physiological and pathological signals. Axons are more efficiently insulated in myelinated fibers, where segments of the axonal membrane are wrapped by the myelin sheath. Although extensive data are available on the electrical properties of myelin, its structural and mechanical characteristics—as well as the role of its lipid composition—are also relevant, although much less explored. The objective of our review is derived from this point since alterations in lipid components can lead to axonal dysfunction, giving rise to neurological disorders such as multiple sclerosis and other demyelinating conditions. In this review, concerning the lipid composition of myelin, we focus on two distinct classes of lipids: sphingolipids and long-chain fatty acids, emphasizing the differential contributions of saturated versus polyunsaturated species. We analyze studies that correlate the mechanical vulnerability of myelin with its lipid composition, particularly sphingomyelin, thereby underscoring its role in protecting neurons against physical stress and providing a robust microstructural network that reinforces the white matter as a whole. From a biochemical perspective, we examine the susceptibility of myelin to oxidative stress, metabolic disorders, and extreme nutritional deficiencies in relation to the role of long-chain fatty acids. Both perspectives highlight that the aforementioned lipids participate in a complex biomechanical balance that is essential for maintaining the stability of myelin and, consequently, the integrity of the central and peripheral nervous systems.

The present study investigates a multicomponent lipid system that simulates the neuronal grey matter membrane, employing molecular acoustics as a precise, straightforward, and cost-effective methodology. Given the significance of omega-3 polyunsaturated fatty acids in the functionality of cellular membranes, this research examines the effects of reducing 1-palmitoyl-2-docosahexaenoylphosphatylcholine (PDPC) content on the compressibility and elasticity of the proposed membrane under physiological conditions. Our results align with bibliographic data obtained through other techniques, showing that as the proportion of PDPC increases in the grey matter membrane model, the system’s compressibility decreases, and the membrane’s elasticity increases, as evidenced by the reduction in the bulk modulus. These results could be interpreted in light of the emerging model of lipid rafts, in which esterified DHA infiltrates and remodels their architecture. We contend that the results obtained may serve as a bridge between biophysics and cellular biology.

In this study, we present a multicomponent lipid model membrane composed of six lipids, in-cluding cholesterol, which represent the structure of neuronal membranes found in grey matter. To our knowledge, no previous studies have attempted a model like this. We constructed our model membranes using an esterified form of the most abundant polyunsaturated fatty acid found in grey matter: docosahexaenoic acid (DHA). It is the most prevalent fatty acid in the brain and is essential for maintaining cellular structural integrity, acting as a major phospholipid in neural membranes. The aim of this work is to analyse the effects that different proportions of DHA have on the proposed membrane model. For this purpose, transmission electron microscopy, zeta potential, and molecular acoustics were used. The results showed differences that may be attributable to the influence DHA has on the nanodomains of sphingomyelin and cholesterol.