Control of Adhesion and Fusion of Model Myelin Bilayers Using Structured Polymers

Control of adhesion and fusion of model myelin bilayers using structured polymers

Xavier Banquy, Kai Kristianson, Dong Woog Lee and Jacob Israelachvili

Department of Chemical Engineering, University of California, Santa Barbara, USA

The myelin sheath is formed by extensions of oligodendrocyte cell membranes that wrap around the axon to form a cylindrical scroll a few tens of microns in diameter. 70-80% of the dry weight of myelin consists of lipids, which is significantly higher than most other cell membranes. The sheath consists of repeat units of ‘double' bilayers separated by 3-4 nm thick aqueous layers that alternate between the cytoplasmic and extracellular spaces. Myelin bilayers are asymmetric in composition and structure, with different compositions at the inner (cytoplasmic) and outer (extracellular) monolayers.

Myelin dysfunctions vary from deterioration of signal transduction to demyelinating diseases such as multiple sclerosis (MS). MS is characterized by a change in the lipid composition of the myelin membrane which leads to the appearance of lesions reflecting loss of inter-membrane adhesion. We hypothesize that these processes may be controlled by modifying the molecular interactions between the lipids and proteins in myelin. Polyethylene glycol (PEG) and poloxamers are non-toxic and FDA-approved polymers that have recently been used to successfully treat spinal cord injuries in animals [1-3]. In this presentation we will show that these polymers can act to heal the myelin sheath via adding on an attractive osmotic ‘depletion' force to provide a similar effect that we have recently observed for myelin basic protein [4-5]. The magnitude of the depletion force depends on several physical chemical parameters as the concentration, the size and structure of the polymer as well as the affinity of the polymer to the bilayer.  
The effect of these parameters on myelin bilayers adhesion will be presented and conclusions will be made about the possible use of these polymers as a possible “treatment” that could lead to the prevention or reversal of swelling and vacuolization of myelin that accompanies MS.

References:

[1] Borgens, R., D. Bohnert, B. Duerstock, D. Spomar, R. C. Lee, 2004. Subcutaneous tri-block copolymer produces recovery from spinal cord injury. J. Neuroscience Res. 76:141-154

[2] Borgens, R. B., D. Bohnert, 2001. Rapid recovery from spinal cord injury after subcutaneousladministered polyethylene glycol. J. Neuroscience Res. 66: 1179-1186.

[3] Luo, J., R. Borgens, R. Shi, 2004. Polyethylene glycol improves function and reduces oxidative stress in synaptosomal preparations following spinal cord injury. J. Neurotrauma 21:994-1007

[4] Y Hu, I Doudevski, D Wood, M Moscarello, C Husted, C Genain, J A Zasadzinski, and J Israelachvili, “Synergetic interactions of lipids and myelin basic protein”, Proceedings of National Academy of Sciences 101 (2004) 13466-13471.

[5] Y Min, K Kristiansen, J M Boggs, C Husted, J A Zasadzinski, and J Israelachvili, “Interaction forces and adhesion of supported myelin lipid bilayers modulated by myelin basic protein”, Proceedings of National Academy of Sciences 106 (2009) 3154-3159.