Cationic Liposome-Microtubule Complexes: Pathways to the Formation of Two-State Lipid-Protein Nanotubes with Open or Closed Ends

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Original entry: Naveen Sinha, APPHY 226, Spring 2009

Cationic Liposome-Microtubule Complexes: Pathways to the Formation of Two-State Lipid-Protein Nanotubes with Open or Closed Ends.

Uri Raviv, Daniel J. Needleman, Miguel Ojeda-Lopez, Herbert P. Miller, Leslie Wilson, Cyrus R. Safinya

Proceedings of the National Academy of Sciences, Track II, August 2005, 102, 11167-11172

Soft matter keywords: Polyelectrolyte, Lipid complex, Membrane, Tubulin, Vesicles, Beads on a rod

Summary

Interactions between electrically charged lipids and biopolymers are utilized for numerous cell processes, such as transporting the contents of vesicles into a cell (e.g. endocytosis, drug delivery, and gene therapy). The authors study a range of cationic lipids with anionic tublin dimers. Previous researchers only studied the case in which the the membrane curvature was much larger than the reciprocal of the polyectrolyte diameter. In the present study, the authors examine the case when the spontaneous curvature of the lipid membrane is comparable to the "curvature" of the tubulin molecules (twice the reciprocal of the polyelectrolyte diameter). Depending on the relative concentrations of lipids and tubulin molecules, a nanotububle forms with either open or closed ends. Since positively charged lipids are commonly used for encapsulating genes and drugs into cells, the results from the present study could be extended to novel, non-viral delivery systems.

Soft Matter Concepts

The present study is an example of exploring the phase space of a liposome-microtubule complex. The lipids are positively charged and interact electro-statically with negatively charged tubulin molecules. By varying the rigidity of the components, the charge density of the membrane, and the ratio of charged lipids to tubulin dimers, an assortment of shapes can be produced, as illustrated in the flow chart below:

RavivFlowChart.jpg

As mentioned above, previous studies only looked at the case in which the polyectrolyte "curvature" was much more than the spontaneous curvature. If the elastic energy of the lipid membrane is large compared to thermal energy, the system can form either parallel sheets (i.e. lipid membranes alternating with a polyectrolyte like DNA) or a hexagonal lattice (e.g lipid membranes wrapped around DNA molecules aligned along the lattice). If the membrane elastic energy is comparable to the thermal energy, then only the hexagonal morphology forms.

The current system also depends on the value of the thermal energy. For high elasticities, the lipids take on a "beads on a rod" appearance. If the elastic energy is about 10 times the thermal energy, the lipid surrounds the tubulin, creating a nanowire. The nanowire can have either closed or open ends, depending on the relative amount of charged to neutral lipids. If fewer of the lipids are charged (< 10%), then the system starts as "beads on a rod" before wetting the tubulin rod and forming closed ends. If more of the lipid are charged, or if the elastic energy is less, then the ends of the nanotube are opnen.

The following set of TEM images provides the evidence for each of these morphologies:

RavivTEM.jpg

The top image shows a microtubule polymer, without any lipid, as a control. If the fraction of charged lipids is less than 0.1, then the system is kinetically trapped and forms on a "beads on a rod" morphology that can take 60 hours to decay. Above this critical concentration, the ratio of lipids to tubulin determines whether or not the nanotube has open or closed ends.

The authors suggest that the observations in this study are generalizable to other soft matter systems, many of which had biomedical applications.

written by: Naveen N. Sinha