Which is better, a quick vertical jab on the buttock or the delicately soft entry of a blood sample? Waiting to find out "for what," some are already wondering "how" to use those tiny "molecular syringes" which are carbon nanotubes. With a diameter of less than one millionth of a millimetre (nanometre) and a maximum length of just a few millimetres, the first use that springs to mind when we think of this ethereal tubes -- the smallest ever made by man -- is as potential needles for injecting drugs or genes into sick cells. And if a syringe it is, we had better start thinking about how to use them.
A group of researchers at the Ciamician department of the University of Bologna (Unibo, Italy) has no doubt about it. The easiest and most natural way of penetrating a cell membrane with a carbon nanotube, in its simplest form, is at an angle which is almost flat against the membrane surface. Just as a nurse does to "find" a vein.
Siegfried Höfinger (Unibo) explains: "A flat entry offers the most favourable energy balance." The entry of the nano-needle is in fact twice as easy than at an angle of, say, 45°, and three times easier than vertical penetration. "We can even hypothesise that the nanotube takes on this position of its own free will when placed near the membrane," adds Tommaso Gallo, another of the young authors working on the study, which is in press in the scientific journal Biomaterials.
The scientists' doubts lie in the extreme difficulty in handling such small objects. "Probably no one is able to experimentally verify these phenomena yet," says Höfinger. The chemists from Bologna, part of Francesco Zerbetto's research group, have drawn their conclusions not from physical experiments but from theoretical simulations. Mathematical models which consider all the forces at stake and the physical and chemical properties of the elements involved, predicting their behaviour.
The encouraging aspect of the Unibo research, which also saw the participation of the Michigan Technological University and the Universidade do Porto, is that two independent simulations based on completely different theoretical approaches led to an identical response. Flat entry into the membrane is certainly preferable. The first simulation was based on the system's energy balance and the concept of "environmental free energy." The second simulation, on the other hand, is typically used to describe the behaviour of large molecules in solutions (solvents and polymers). It may be less accurate than the first, but it has the advantage of illustrating the dynamic and temporal evolution of the described phenomenon well.
To simplify the problem, the researchers considered the use of very short tubes, maximum 7 nanometres long, which could be fully included in the cell wall, which is around 5 nanometres thick. It was also seen that, once inside the membrane, the longer tubes tend to lie longitudinally, parallel to the surface. Carrying out the test with bundles of smaller tubes bound together, it was also demonstrated that compact bundles of tubes bound tightly to each other cause less cell damage.
The future that Höfinger sees for the nanotubes is not however that of molecular syringes, but of probes. Their physical properties, including their great electrical and thermal conductivity, make them particularly suited for exchanging information between the inside and outside of the cell. They may therefore also be used to test for certain substances and test certain processes beyond cell membranes. Probes or syringes, the scientist in any case feel comfortable in their role as molecular nurses, and are eager to keep on testing using all the new tools of the trade.
- Siegfried Höfinger, Manuel Melle-Franco, Tommaso Gallo, Andrea Cantelli, Matteo Calvaresi, José A.N.F. Gomes, Francesco Zerbetto. A computational analysis of the insertion of carbon nanotubes into cellular membranes. Biomaterials, 2011; DOI: 10.1016/j.biomaterials.2011.06.011
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