New Nanoscale Imaging May Lead to New Treatments for Multiple Sclerosis

A new method of nanoscopic imaging may lead to experimental methods for early detection and diagnosis — and to possible treatments — for pathological tissues that are precursors to multiple sclerosis and similar diseases.

Chemical engineers at the University of California, Santa Barbara, have studied the myelin sheath, the membrane surrounding nerves that is compromised in patients with multiple sclerosis. The study was published in this week’s online edition of the Proceedings of the National Academy of Sciences.

These are fluorescence images of lipid domains in model (laboratory reconstituted) myelin monolayers showing coexistence of liquid-ordered (dark) and liquid-disordered (pseudocolored) phases. Depending on the conditions (e.g., lipid composition, surface pressure, temperature), the lipid domains can exist in various shapes, including striped (left) and circular (right). (Image: Younjin Min, MIT)

“Myelin membranes are a class of biological membranes that are only two molecules thick, less than one-millionth of a millimeter,” co-author Jacob Israelachvili said. “The membranes wrap around the nerve axons to form the myelin sheath.”

The way different parts of the central nervous system, including the brain, communicate with each other throughout the body is via the transmission of electric impulses along the fibrous myelin sheaths, Israelachvili explained. The sheaths act like electric cables or transmission lines.

Shown is an illustration of a neuron, which is the basic functional unit of the nervous system. Enlarged portion indicates myelin sheath, which is a multilamellar membrane surrounding the axon of neurons. (Image: Dottie McLaren)

“Defects in the molecular or structural organization of myelin membranes lead to reduced transmission efficiency,” he said. "This results in various sensory and motor disorders or disabilities, and neurological diseases such as multiple sclerosis.”

At the microscopic and macroscopic level, multiple sclerosis is characterized by the appearance of lesions or vacuoles in the myelin; this eventually results in the complete disintegration of the myelin sheath in a process called demyelination.

Dong Woog Lee (left) and Jacob N. Israelachvili are researchers at the University of California, Santa Barbara. (Image: Rod Rolle)

The article describes fluorescence imaging and other measurements of domains, which are small heterogeneous clusters of lipid molecules — the main constituents of myelin membranes — that are likely to be responsible for the formation of lesions. The researchers did this using model molecular layers in compositions that mimic both healthy and diseased myelin membranes.

They observed differences in the appearance, size and sensitivity to pressure of domains in the healthy and diseased monolayers. Next, they developed a theoretical model, in terms of certain molecular properties, that appears to account quantitatively for their observations.

“The discovery and characterization of micron-size domains that are different in healthy and diseased lipid assemblies have important implications for the way these membranes interact with each other,” Israelachvili said. “And this leads to new understanding of demyelination at the molecular level.”

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