Kirsi Pakkanen et al 2009 Phys. Biol. 6 046004 doi:10.1088/1478-3975/6/4/046004
Desipramine induces disorder in cholesterol-rich membranes: implications for viral trafficking
Kirsi Pakkanen1, Emppu Salonen2, Anna R Mäkelä1,5, Christian Oker-Blom1,6, Ilpo Vattulainen2,3,4 and Matti Vuento1
Show affiliationsIn this study, the effect of desipramine (DMI) on phospholipid bilayers and parvoviral entry was elucidated. In atomistic molecular dynamics simulations, DMI was found to introduce disorder in cholesterol-rich phospholipid bilayers. This was manifested by a decrease in the deuterium order parameter SCD as well as an increase in the membrane area. Disordering of the membrane suggested DMI to destabilize cholesterol-rich membrane domains (rafts) in cellular conditions. To relate the raft disrupting ability of DMI with novel biological relevance, we studied the intracellular effect of DMI using canine parvovirus (CPV), a virus known to interact with endosomal membranes and sphingomyelin, as an intracellular probe. DMI was found to cause retention of the virus in intracellular vesicular structures leading to the inhibition of viral proliferation. This implies that DMI has a deleterious effect on the viral traffic. As recycling endosomes and the internal vesicles of multivesicular bodies are known to contain raft components, the effect of desipramine beyond the plasma membrane step could be caused by raft disruption leading to impaired endosomal function and possibly have direct influence on the penetration of the virus through an endosomal membrane.
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Issue 4 (December 2009)
Received 24 June 2009, accepted for publication 17 August 2009
Published 10 September 2009
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Desipramine induces disorder in cholesterol-rich membranes: implications for viral trafficking
Kirsi Pakkanen et al 2009 Phys. Biol. 6 046004
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Neural prostheses and brain plasticity
James B Fallon et al 2009 J. Neural Eng. 6 065008
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