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Carbon Nanotube Syringes. Joe Yeager. Introduction. Major obstacle in drug delivery: how to get specific drugs across the cell membrane? If membrane is not permeable to the drug, it may not achieve the desired effect
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Carbon Nanotube Syringes Joe Yeager
Introduction • Major obstacle in drug delivery: how to get specific drugs across the cell membrane? • If membrane is not permeable to the drug, it may not achieve the desired effect • With better permeability, lower concentrations of drugs would be necessary, limiting side effects greatly • Better targeting to specific areas of the body
The Cell Membrane • Fluid mosaic: flexible and varied structure • Consists of phospholipids (DMPC) • Hydrophilic head • Hydrophobic tail
Transport Across A Membrane • Cell membranes must have a way to allow certain molecules to pass through • Generally accomplished by proteins • Allow metal cations (i.e. Ca2+, Na+, K+), anions (i.e. Cl-) as well as other molecules to permeate the membrane • Proteins specifically designed to transport particular molecules
Carbon Nanotubes • Sheets of graphite (hexagonal lattice) rolled into tubes • Exceedingly strong • Properties vary greatly with length, diameter, and configuration (especially twist) • Identified in 1991 by S. Iijima when passing fullerenes through an electric arc • Can be capped at end • Can be single-walled or multiple-walled • Can have one of three different structures depending on how graphite sheet is “rolled”
Nanosyringe Design • Carbon nanotube created with particular size and properties to accommodate a certain molecule • Nanotube body is nonpolar • Ends affixed with polar caps • “Chaperone” lipids used to help the nanosyringe move into position in the membrane
Molecular Dynamics • Computer simulation of molecules • Can accurately predict interactions even between very large molecules • Unfortunately, takes a great deal of time • Takes into account mechanics, thermodynamics, electrical charges and polarity, and even quantum mechanical factors • Often used to understand folding of proteins
Nanosyringe Simulation A: basic nonpolar nanotube B: nanotube with polar ends C: molecular model of membrane phospholipid D: simplified MD model of membrane phospholipid
Nanosyringe Findings • Nanotubes with polar caps will insert themselves into a phospholipid bilayer membrane • Once in place, nanotube can conduct molecules (i.e. water) across the membrane • In order for the nanotube to stay in place, polar caps must be present on the nonpolar body • Otherwise the tube rotates and lipid tails enter the openings of the tube • This prevents conduction across the membrane
Nanotube Self-Alignment Nanosyringe begins near cell membrane
Nanotube Self-Alignment Nanotube is absorbed into membrane
Nanotube Self-Alignment Polar-polar and nonpolar-nonpolar sections of membrane and nanotube start to align
Nanotube Self-Alignment Nanotube fully aligns with cell membrane
Chaperone Lipids • (Marked in Orange above) • Attach to one end of the nanosyringe from the near phospholipid layer • Move along with one end of nanosyringe to help guide it through the phospholipid bilayer • Once movement is complete, chaperone lipids are integrated into far phospholipid layer
Future Directions • Bacterial membranes are negatively charged, while human membranes are neutral • Nanosyringes could selectively target bacteria, leaving human cells alone • Different types of nanotubes with varying attached groups could selectively transport molecules across a membrane • Nanosyringes could operate like enzymes, with a very specific template for molecules to be transported
Sources • Adams, Thomas A. “Physical Properties of Carbon Nanotubes.” http://www.pa.msu.edu/cmp/csc/ntproperties/ • Dalton, Mark. “Cell Membranes.” http://www.cbc.umn.edu/~mwd/cell_www/chapter2/membrane.html • Lopez, Carlos F., Nielsen, Steve O., Moore, Preston B., and Klein, Michael L. “Understanding Nature’s Design for a Nanosyringe.” http://www.pnas.org/cgi/content/full/101/13/4431 • Travis, J. “New Antibiotics Take Poke at Bacteria.” Science News http://wilsontxt.hwwilson.com/pdfhtml/00744/P16QI/ZS4.htm