For a healthy nervous system, axons—the long projections of our nerve cells that run throughout our bodies—must be properly insulated.
Much like conventional power cords need electrical insulators around the conducting wires for efficient and effective transfer of current, axons rely on multiple bilayers of myelin to maintain a rapid and optimal transfer of impulses between, for instance, brain and organ, or spinal cord and muscle. These bilayers are composed of lipids (fat molecules), protein, and water.
“Basically, myelin is this multiple stacking of lipid bilayers,” says Dong-Woog Lee, a researcher in the chemical engineering department at the University of California, Santa Barbara. “They need to be compact, and with very little water between the bilayers.”
Lee and colleagues found that even the slightest change in the composition of these myelin bilayers affect their ability to insulate axons. Their findings could offer insights into demyelinating diseases, such as multiple sclerosis.
Stick like glue
To observe and measure the characteristics and differences between healthy and diseased myelin bilayers, they studied the ability of these layers to adhere to each other.
The researchers used a highly sensitive instrument, called the surface forces apparatus, that can measure interactions between membranes. The deposited a lipid bilayer on a mica substrate on each of the two opposing surfaces of the apparatus.
Then they immersed the setup in a buffer solution containing myelin basic protein (MBP), a biomolecule commonly found in myelin that gives them adhesive properties and plays a role in maintaining the optimal structure of the myelin sheath.
They brought the two bilayers close together, allowing them to stick to each other, and then pulled them apart, measuring the strength of the adhesion brought about by the MBP “glue” between the bilayers, and also the MBP’s adsorption—the ability of the MBP molecules to stick to the bilayers’ surfaces.
They performed this experiment with both healthy myelin and with “disease-like” myelin bilayers.
“A lipid bilayer simulating a normal or healthy myelin membrane adsorbs this protein much better than a lipid bilayer simulating a multiple sclerosis-type of myelin membrane,” says UC Santa Barbara researcher Kai Kristiansen, “meaning that the protein attaches more strongly to the lipid bilayer and can make two apposing lipid bilayers adhere more firmly to each other and at a smaller distance—which is highly desirable for a well functioning myelin around a neuron.”
Swelling and multiple sclerosis
One common characteristic of diseased myelin is swelling, due to various causes such as the autoimmune responses associated with multiple sclerosis and its variants, or in cases of infection or exposure to certain chemicals. Genetics also play a role in the health of myelin.
“When the disease progresses, people can see that they swell and eventually vesiculate, creating scars,” says Lee, who is lead author of the study published in the Proceedings of the National Academy of the Sciences.
The MBP layer between the lipid bilayers also swells with water that seeps in between the double lipid layers. Instead of being a compact, molecule-thick film, the MBP layer becomes more gel-like.
“And since there’s more water between the bilayers, their insulation property decreases,” says Lee. From there, impulses slow down along the axon, or dissipate before they reach their destinations, causing paralysis and loss of function.
Disease–related changes in the lipid domain structures’ size and distribution also causes irregular adsorption of MBP onto the lipid bilayers and weakens their adhesion properties. This in turn also leads to lower nerve insulation.
The next step, according to Jacob Israelachvili, professor of chemical engineering and of materials, is to develop a user-friendly bench-top instrument that could be used in hospitals and clinics to visualize the membranes of certain cells, both healthy and pathological, whose domain structure can be an indicator of the progression of a disease.
“We are currently planning a collaboration with a local hospital to provide us with such membranes, for example, from leukemic blood cells, that we would tag with a suitable fluorescent dye to enable this imaging,” he says.
Source: UC Santa Barbara