The findings were presented at the American Society for Cell Biology's 47th annual meeting, Dec. 3, in Washington, D.C.

By breaking down the individual steps in the biological pathway that sperm use to generate energy, the researchers plan to reproduce that pathway for use in a human-made device.

"Our idea is not the final product but rather an energy-delivery system," said Alex Travis, Cornell assistant professor of reproductive biology at the College of Veterinary Medicine's Baker Institute for Animal Health and the study's senior author.

"As a proof of principle that this kind of strategy could work, we've shown that the first two enzymes could be attached to the same chip and act in series," added Chinatsu Mukai, a postdoctoral associate in Travis' lab and a co-author.

A midsection between the head and the long tail of sperm contains mitochondria, organelles that generate a cell's power.

But sperm have also developed a second energy source to power their long tail.

They employ a process known as glycolysis, which breaks down glucose to derive ATP, which cells use for energy.

The pathway for glycolysis requires 10 enzymes.

Using special "targeting domains," sperm tether these to a fibrous sheath that runs the length of the tail. In this study, the researchers are trying to re-create this glycolytic pathway by modifying each protein's targeting domain so that they can instead bind to nickel ions on a manufactured chip.

So far, they have successfully attached three of the 10 enzymes required to make ATP from glucose, and each has remained functional.

If they manage to attach all 10 enzymes, each enzyme will in principle act in a series to ultimately generate ATP to power a nano-device.

In the body, such a device could conceivably use readily available blood glucose as fuel.

Potential uses include delivery systems loaded with chemo drugs or antibiotics to target specific cells. Such a system would allow doctors to provide steady doses while reducing side effects that result from treating the entire body with a drug.

Travis' group is trying to get funding to complete attaching the rest of the enzymes in the glycolysis pathway. "We have a provisional patent, so if a company shows interest, we could also work something out with them," said Travis.

Since the researchers only plan to re-create the biological pathway used by sperm to create energy, it will require input from bioengineers and different physicians and veterinarians to develop viable delivery systems and other innovative uses, Travis stressed.

Sperm Power: New Tool for Nanobots
Tracy Staedter, Discovery News
Dec. 26, 2007

The tiny biological machine is something like a car engine that uses fuel to generate motion.

Only this machine -- composed of 10 carefully arranged enzymes -- runs on natural sugars, using them to produce an high-energy molecule called adenosine triphosphate, or ATP for short.

In the case of sperm, ATP energizes the tail. But it could also be used in nanorobots that do everything from activate drug-delivery pumps to manufacture missing enzymes necessary for healthy bodily functions.

"We're taking what sperm have already figured out how to do and using it for a nanotechnology application," said Alex Travis, assistant professor of reproductive biology at Cornell University College of Veterinary Medicine in Ithaca, NY.

The enzyme engine was particularly interesting to Travis and his team because, unlike most enzymes that like to stick to squishy cellular matter, these like to stick to the rigid, fibrous structure inside a sperm tail. This can be important for artificial applications.

Enzymes bend, twist and rotate as part of their normal functions. Many enzymes, put inside a manufactured nanobot, would not attach to the device properly. But the sperm tail enzymes naturally work on rigid surfaces; the trick is getting them to stick to manmade devices.

To do that, the researchers changed a part of the enzyme that lets it attach to the fibrous tail structure so that it would attach to nickel ions on a manufactured chip.

So far, they have attached three of the 10 enzymes -- two that are next to each other and one from the middle of the sequence. When attached, the enzymes activate and perform their normal function. If the scientists can get all 10 enzymes to work in sequence, they'll have their biological engine.

On a working device, the enzymes would use the glucose to make ATP, which in turn would power mechanical functions or initiate chemical reactions for therapeutic reasons.

"I think what's really interesting is that it appears to work," said Regina Turner, assistant professor of large animal production at the University of Pennsylvania School of Veterinary Medicine.

But all of the enzymes will need to work together to make the biological engine.

"He will need to show that he can do this with the entire pathway," said Turner.

And if that happens, it will be important to find a way to get the energy from the biological engine to the necessary parts of the nanodevice.

Because the researchers are focused exclusively on building the engine, said Travis, bioengineers will eventually need to solve the energy-delivery problem.

Department of Chemistry and Kanbar Laboratory for Nanomaterials, Center for Advanced Materials and Nanotechnology, Bar-Ilan University, Ramat-Gan 52900, Israel.

Magnetite nanoparticles conjugated to protein are developed in order to potentially serve as protein carriers into bovine sperm cells. The conjugate comprises iron oxide nanoparticles that are covalently bound to an anti-protein kinase C (PKC)alpha antibody. This conjugate can serve for cellular PKC localization and the inhibition of its function. The surface of the nanoparticle is first modified with (3-aminopropyl) thrimethoxysilane to form a self-assembled monolayer, and subsequently conjugated with the antibody through amidation between the carboxylic acid end groups on the antibody and the amine groups on the surface of the nanoparticles. The anti-PKCalpha localization is proven by fluorescent microscopy and iron staining. The activity of the anti-PKCalpha conjugated with the nanoparticle is tested by recognizing PKCalpha using the Western blot method.