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.
- PACS
- Subjects
- Dates
-
Issue 4 (December 2009)
Received 24 June 2009, accepted for publication 17 August 2009
Published 10 September 2009
-
-
Desipramine induces disorder in cholesterol-rich membranes: implications for viral trafficking
Kirsi Pakkanen et al 2009 Phys. Biol. 6 046004
-
An optimal state estimation model of sensory integration in human postural balance
Arthur D Kuo 2005 J. Neural Eng. 2 S235
-
Heat kernel coefficients for compact fuzzy spaces
Naoki Sasakura JHEP12(2004)009
-
The Behavior of Novae Light Curves Before Eruption
Andrew C. Collazzi et al. 2009 The Astronomical Journal 138 1846
-
Gain degradation of lead-type channel electron multipliers in ultra-high vacuum
F D G Bennett and D G Thorpe 1970 J. Phys. E: Sci. Instrum. 3 241
-
Alternating current potential-drop measurement of the depth of case hardening in steel rods
John R Bowler et al 2008 Meas. Sci. Technol. 19 075204
-
Evidence for graphene growth by C cluster attachment
Elena Loginova et al 2008 New J. Phys. 10 093026
-
Subaru/COMICS Study on Silicate Dust Processing around Young Low-Mass Stars
Mitsuhiko Honda et al. 2006 ApJ 646 1024
-
A lattice approach to spinorial quantum gravity
P Renteln and L Smolin 1989 Class. Quantum Grav. 6 275
-
The CMS experiment at the CERN LHC
The CMS Collaboration et al 2008 JINST 3 S08004
Users also read
What's this?- Accurate particle-based simulation of adsorption, desorption and partial transmission
- Comparative analysis of rigidity across protein families
- Flux networks in metabolic graphs