Interaction forces and adhesion of supported myelin lipid bilayers modulated by myelin basic protein

Abstract

Force-distance measurements between supported lipid bilayers mimicking the cytoplasmic surface of myelin at various surface coverages of myelin basic protein (MBP) indicate that maximum adhesion and minimum cytoplasmic spacing occur when each negative lipid in the membrane can bind to a positive arginine or lysine group on MBP. At the optimal lipid/protein ratio, additional attractive forces are provided by hydrophobic, van der Waals, and weak dipolar interactions between zwitterionic groups on the lipids and MBP. When MBP is depleted, the adhesion decreases and the cytoplasmic space swells; when MBP is in excess, the bilayers swell even more. Excess MBP forms a weak gel between the surfaces, which collapses on compression. The organization and proper functioning of myelin can be understood in terms of physical noncovalent forces that are optimized at a particular combination of both the amounts of and ratio between the charged lipids and MBP. Thus loss of adhesion, possibly contributing to demyelination, can be brought about by either an excess or deficit of MBP or anionic lipids.biomembrane adhesion ͉ lipid-protein interactions ͉ multiple sclerosis ͉ myelin membrane structure ͉ experimental allergic encephalomyelitis T he myelin sheath is a multilamellar membrane surrounding the axons of neurons in both the central nervous system (CNS) and peripheral nervous system (PNS) (1) as shown in Fig. 1 A and B. The myelin sheath consists of repeating units of double bilayers separated by 3-to 4-nm-thick aqueous layers that alternate between the cytoplasmic and extracellular faces of cell membranes (2) (Fig. 1C). Dehydrated myelin is unusual in that it is composed of 75-80% lipid and 20-25% protein by weight, compared with Ϸ50% of most other cell membranes (3) (Fig. 1 C and D). Multiple lipids make up the myelin sheath (Table 1), and each sheath, with its own distinct physical properties, contributes to the structure, adhesive stability, and possibly the pathogenesis of the myelin membrane. The asymmetric distribution of lipid composition on the cytoplasmic and extracellular faces likely also plays an important role (4). Myelin basic protein (MBP) constitutes 20-30% of total protein by weight and is located only between the 2 cytoplasmic faces, where it acts as an intermembrane adhesion protein.The myelin sheath acts as an electrical insulator, forming a capacitor surrounding the axon, which allows for faster and more efficient conduction of nerve impulses than unmyelinated nerves (5). According to cable theory, the time to transmit a signal over a distance x is ϭ 1 ⁄2RC myelin x 2 , where R is the resistance per unit length, and C myelin is the capacitance between the axon and its surroundings, which is given by (5) C myelin ϭ 2 0 myelin log͑R O /R I ͒ per unit length,where R O and R I are the outer and inner radii (Fig. 1B), 0 is the permittivity of free space, and the mean dielectric constant of the myelin sheath iswhere (Fig. 1C). Low capacitance necessitates a low value of myelin , which is promoted by the much l...

Structural Transition in Myelin Membrane as Initiator of Multiple Sclerosis

“…2−6 In myelin sheaths, the membrane becomes compact due to electrostatic interactions between the negatively charged lipids and positively charged myelin basic protein (MBP). 7,8 MBP, which represents about 10% of myelin by weight, is intrinsically disordered in solution. 9,10 When bound to a lipid surface, secondary structural elements form, and the hydrophobic parts of the protein are embedded in the bilayer.…”

Lipid domains control myelin basic protein adsorption and membrane interactions between model myelin lipid bilayers

“…However, studies have shown that the MBP charge component composition, as well as the balance between charged lipids and MBP charge components, changes in EAE (as well as in MS) tissues (20,21). Other studies (9,15) demonstrated the importance of the hydrophobic interaction between MBP and lipid membranes by showing that MBP specifically binds to lipid domain boundaries (defects), altering the lateral organization of the model myelin bilayers. A recent study also showed that MBP's association with the cytoplasmic leaflet of the myelin membrane induces a phase transition into a cohesive mesh-like protein network (22,23).…”

“…A wellstudied and accepted animal model for MS is the experimental allergic encephalomyelitis (EAE) of the marmoset (2,6). Using this model, recent studies conducted with the surface forces apparatus (SFA) have shown that a loss of adhesion force (7) and structural changes of model membranes with lipid composition characteristic of myelin accompanied compositional alterations of the lipid species (8), as well as an electric charge imbalance between lipid molecules and MBP (9). These alterations also change the lateral distribution and stability of phase-separated lipid domains (or rafts) within model myelin membranes (8,10).…”

“…The predominant size and charge isoform of MBP in healthy and mature myelin has a molecular weight of 18.5 kDa and a net positive charge of 19 (12, 13). Several studies conducted with model and extracted myelin bilayers (9,(14)(15)(16)(17)(18)(19) showed that because of its high content of positively charged residues, MBP binds to the negatively charged lipids of the cytoplasmic leaflets of the bilayer via electrostatic interaction in addition to hydrophobic interactions. However, studies have shown that the MBP charge component composition, as well as the balance between charged lipids and MBP charge components, changes in EAE (as well as in MS) tissues (20,21).…”

Effect of Cornus officinalis glycosides on the myelin basic protein in blood serum and the nerve function in Balb/c mice after sciatic nerve injury

“…MBP is the main protein of myelin sheath and it has neural specificity. Under normal physiological condition, its content in serum is extremely low [3][4]. After peripheral nerve injury, the parclose between nervus vascularis is damaged and the expression quantity of MBP in blood volume increases rapidly, so the different expressions of MBP can dynamically observe the situation of myelin damage and repairing [5].…”