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Abstract
The myelin sheath—a multi-double-bilayer membrane wrapped around axons—is an essential part of the nervous system which enables rapid signal conduction. Damage of this complex membrane system results in demyelinating diseases such as multiple sclerosis (MS). The process in which myelin is generated in vivo is called myelination. In our study, we investigated the adhesion process of large unilamellar vesicles with a supported membrane bilayer that was coated with myelin basic protein (MBP) using time-resolved neutron reflectometry. Our aim was to mimic and to study the myelination process of membrane systems having either a lipid-composition resembling that of native myelin or that of the standard animal model for experimental autoimmune encephalomyelitis (EAE) which represents MS-like conditions. We were able to measure the kinetics of the partial formation of a double bilayer in those systems and to characterize the scattering length density profiles of the initial and final states of the membrane. The kinetics could be modeled using a random sequential adsorption simulation. By using a free energy minimization method, we were able to calculate the shape of the adhered vesicles and to determine the adhesion energy per MBP. For the native membrane the resulting adhesion energy per MBP is larger than that of the EAE modified membrane type. Our observations might help in understanding myelination and especially remyelination—a process in which damaged myelin is repaired—which is a promising candidate for treatment of the still mostly incurable demyelinating diseases such as MS.
Highlights
The biological membrane is an important component of cellular function and metabolism
We report on the adhesion mechanisms of large unilamellar vesicles (LUV) onto a supported membrane that was coated with an myelin basic protein (MBP) layer
Adhesion of LUV with local formation of a second membrane bilayer results in an MBP layer that is reduced in thickness
Summary
The biological membrane is an important component of cellular function and metabolism. Investigation of biological membrane components, characterization of their physico-chemical properties and the study of their interactions with membrane binding proteins can answer important questions that are central for human health and disease. Myelin Membrane Adhesion Mechanism cells in the human brain, for instance, results in nerve conduction failure and neurodegeneration (Love, 2006; Weil et al, 2016). While the native lipid composition occurs in healthy cytoplasmic myelin sheaths, the diseased lipid composition has been found in animals having experimental autoimmune encephalomyelitis (EAE), which is an animal model to study diseases such as e.g., MS that are connected to demyelination (Ohler et al, 2004). We found a direct connection between the bending stiffness of large unilamellar vesicles (LUV) having either EAE-diseased or native-like lipid composition and the formation of multilamellar structure which is mediated by the binding strength of MBP with the respective membrane types (Krugmann et al, 2020b)
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