(569d) 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.