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January 23, 2017

Sperm Tails Inspire Highly Efficient Enzyme Reaction Mechanism

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The very cells that created us may have a role in saving our lives.

Scientists have always been amazed by the energy production system in a sperm’s tail. The system drives flagellar movement and is extremely efficient, like a high-speed vehicle with a self-charging system, independent of external energy sources.

Now, Cornell researchers are mimicking such a system in the hopes of advancing fields such as human and animal health. They hope to use their findings to create implantable medical devices that utilize blood sugar to make products as well as support in drug delivery.

“Mammalian sperm have highly efficient energy production systems in their tails,” said Chinatsu Mukai, postdoc at Cornell’s Travis Lab of Reproduction, Nanotechnology and Conservation. “We have been studying this system and have been amazed at how nature creates such an efficient, reasonable and flawless system to drive flagellar movement.”

Inspired by this structure, the Travis Lab has engineered a system of 10 glycolytic enzymes tethered via oriented immobilization to nanoparticles. Glycolytic enzymes are enzymes used in glycolysis, a process that creates energy for the cell. Oriented immobilization is fixing the position of an entity, in this case the enzymes.

The lab team’s goal was to mimic the sperm tail’s energy production system to create an organic-inorganic device that can provide energy to further processes such as glycolysis — the process that creates energy for the cell.

The result, when compared to that of other non-tethered enzymes, was a significant increase in the efficiency of reactions to convert glucose to lactate. This system of enzyme organization provides proof of the principle that complex biological pathways can be reproduced in hybrid organic-inorganic systems.

Mukai uses the analogy of baking a cake to explain her study.

“Think about decorating a cake,” Mukai said. “It takes 10 steps. It is much faster to make the cake if all the steps happen in one place. In a cake assembly line, all steps are in one kitchen; from measuring flour to finishing icing, everything is very efficient. In sperm, all 10 enzymes are tethered to the cytoskeletal element  — the kitchen — so that each enzyme passes intermediate molecules to the next enzyme much faster.”

By having all the enzymes needed for production close to one another, i.e. via tethering, these processes are faster those that of non-tethered enzymes.

“In other [non-tethered enzyme] cells, these 10 enzymes are floating freely inside the cell, meaning that intermediate molecules are passed slowly from one enzyme to the next,” Mukai explained. “Imagine that each step is performed on a single boat floating in Cayuga lake. To move on to the next step, the next boat has to be found from hundreds of boats floating in the lake. Since sperm enzymes carry ‘tags’ for tethering, the sperm model allowed us to tether these enzymes without interfering in their activities. Thus, they provided higher efficiency of making a final product compared to the enzymes in a non-tethered solution.”

Higher enzyme production can have numerous advantages.

“It takes less substrate and time to make a final product,” Mukai said. “In addition, these tethered enzymes are portable so any kind of material can be used for the tethering scaffold.”

Mukai admits that, due to differences in nature and man-made models, her work on tethered enzymes is incomplete.

“We haven’t completed the entire glycolytic pathway,” Mukai said. “One enzyme, triose phosphate isomerase, is still missing because the engineered enzyme didn’t work the way the nature model does. “

She explains that the path of future research depends on whether or not the missing enzyme can be replicated.
“We would like to find out how TPI is regulated in an actual cell so that we can complete the entire glycolytic pathway,” Mukai said. “This energy-producing pathway can be combined to any kind of biological reaction that needs energy.”