New cationic lipids form channel-like pores in phospholipid bilayers.
Two representatives of a new class of cationic lipids were found to have high pore-forming activity in planar bilayer membranes. These molecules, called BHHD-TADC and BHTD-TADC, have qualitatively similar effects on phospholipid membranes. Addition of 2.5-5 micro M of either of them to the membrane bathing solutions resulted in formation of long-lived anion-selective pores with conductance in the range 0.1-2 nS in 0.1 M KCl. Pore formation was found to be dependent on the potential applied to the membrane. When negative potential was applied to membrane at the side of addition, the rate of pore formation was much lower compared to when the positive potential was applied. Dependence of pore formation on compound concentration was highly nonlinear, indicating that this process requires assembly of molecules in the membrane. Addition of any of these compounds on both sides of the membrane increased the efficiency of pore formation by one to two orders of magnitude. Pore formation was strongly pH dependent. Although pores were formed with high efficiency at pH 6.5, only occasional fluctuations of membrane conductance were observed at pH 7.5. Possible mechanisms of new compounds biological activity are discussed.
Chanturiya
Alexandr
A
Genetic Therapy, Inc., Gaithersburg, MD 20878, USA.
Yang
Jingping
J
Scaria
Puthupparampil
P
Stanek
Jaroslav
J
Frei
Joerg
J
Mett
Helmut
H
Woodle
Martin
M
D002412:Cations / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004553:Electric Conductivity; D005233:Fatty Alcohols / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000737:chemistry*; D008051:Lipid Bilayers / Q000138:chemical synthesis / Q000737:chemistry*; D008560:Membrane Fluidity; D008564:Membrane Potentials / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D010743:Phospholipids / Q000737:chemistry*; D016062:Porosity; D011437:Propylamines / Q000737:chemistry*
C478377:5,18-bis(2-hydroxyhexadecyl)-1,5,18,22-tetraazadocosane; C478378:5,18-bis(2-hydroxytetradecyl)-1,5,18,22-tetraazadocosane; D002412:Cations; D005233:Fatty Alcohols; D007473:Ion Channels; D008051:Lipid Bilayers; D010743:Phospholipids; D011437:Propylamines