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Published online on July 29, 2005, 10.1073/pnas.0502183102

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Applied Physical Sciences
Cationic liposome-microtubule complexes: Pathways to the formation of two-state lipid-protein nanotubes with open or closed ends

( polyelectrolyte lipid complexes | small angle x-ray scattering | nanotube-based drug delivery | membrane | tubulin )

Uri Raviv *{dagger}{ddagger}{sect}¶, Daniel J. Needleman *{dagger}{ddagger}{sect}, Youli Li *{dagger}{ddagger}{sect}, Herbert P. Miller {ddagger}{sect}, Leslie Wilson {ddagger}{sect}, and Cyrus R. Safinya *{dagger}{ddagger}{sect}

Departments of *Materials, {dagger}Physics, and {ddagger}Molecular, Cellular, and Developmental Biology, {sect}Biomolecular Science and Engineering Program, University of California, Santa Barbara, CA 93106

Edited by Michael E. Fisher, University of Maryland, College Park, MD, and approved June 14, 2005 (received for review March 17, 2005)

Intermolecular interactions between charged membranes and biological polyelectrolytes, tuned by physical parameters, which include the membrane charge density and bending rigidity, the membrane spontaneous curvature, the biopolymer curvature, and the overall charge of the complex, lead to distinct structures and morphologies. The self-assembly of cationic liposome-microtubule (MT) complexes was studied, using synchrotron x-ray scattering and electron microscopy. Vesicles were found to either adsorb onto MTs, forming a "beads on a rod" structure, or undergo a wetting transition and coating the MT. Tubulin oligomers then coat the external lipid layer, forming a tunable lipid-protein nanotube. The beads on a rod structure is a kinetically trapped state. The energy barrier between the states depends on the membrane bending rigidity and charge density. By controlling the cationic lipid/tubulin stoichiometry it is possible to switch between two states of nanotubes with either open ends or closed ends with lipid caps, a process that forms the basis for controlled chemical and drug encapsulation and release.

Author contributions: U.R. and C.R.S. designed research; U.R. and D.J.N. performed research; U.R., Y.L., H.P.M., and L.W. contributed new reagents/analytic tools; U.R. and C.R.S. analyzed data; and U.R. and C.R.S. wrote the paper.

To whom correspondence may be addressed.

Uri Raviv, E-mail: raviv{at}mrl.ucsb.edu
Cyrus R. Safinya, E-mail: safinya{at}mrl.ucsb.edu

www.pnas.org/cgi/doi/10.1073/pnas.0502183102
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