University of Tübingen: Nanospheres for measuring strength with cell motors

Motor proteins generate the forces for mechanical processes in our cells. On a scale of nanometers, i.e. a millionth of a millimeter, they drive our muscles or, among other things, transport substances within a cell. Erik Schäffer can make such movements visible with the naked eye: the professor for cellular nanosciences at the University of Tübingen follows the work of the molecular machines with specially developed microscopes, “optical tweezers”. His team at the Center for Plant Molecular Biology has now further refined this technology. With higher resolution, special probes, the germanium nanospheres, both movements and the forces of a motor protein can be measured. The results were published in the journal Science released.

With a size of only 60 nanometers, the investigated motor proteins are really tiny, but indispensable for cell processes. Among other things, they help cell division by mechanically pulling chromosomes apart, or they transport “packages” within the cell. If these motor proteins do not work, this can contribute to neurological diseases such as Alzheimer’s in nerve cells, for example.

In order to track down the mechanisms of these molecular machines, biophysicist Erik Schäffer developed ultra-precise optical tweezers. They are based on principles that the astronomer Johannes Kepler discovered in 1609 and for which the physicist Arthur Ashkin received the Nobel Prize in 2018. The radiation pressure of light is used to hold small spheres in place with laser beams and to measure the smallest forces. With this tool, Schäffer has already been able to prove in recent years that the motor protein kinesin, for example, moves around like a dance: With two “feet” it takes eight nanometer steps and a half-turn each time – similar to a Viennese waltz.

His doctoral student Swathi Sudhakar has now further developed the technology of optical tweezers. With so-called germanium nanospheres, much smaller and higher-resolution probes, one can barely reach the five piconewtons strong forces of the biological motors – this corresponds to five trillionths of the weight of a bar of chocolate. This means that even the smallest and quick movements can be measured. So far, these could not be precisely observed because of the jerky heat movement typical of small particles.

Kinesin could be observed in real time and Sudhakar was able to demonstrate another “intermediate step” in his locomotion, which makes the waltz almost perfect. “Whether there is this intermediate step has been discussed among scientists for 20 years,” says Schäffer. “We were able to measure this directly with optical tweezers for the first time.” In addition, the nanospheres revealed a previously unknown “slip mechanism” of the motor protein: “This is a kind of safety line that keeps the motor in the rail if the load is too high” says Schäffer. This mechanism explains the high efficiency of substance transport in cells. “If you know how kinesin motors work in detail, you also better understand the vital cell processes that drive them and malfunctions that can lead to diseases.”

The scientist compares the new technology with an in-depth look, so to speak “under the hood” of the molecular machines. In this way, not only can individual movements of motor proteins be precisely observed, but also a better understanding of how proteins get their structure, for example. “As semiconductors, the nanospheres have other exciting optical and electrical properties and could also be used in other areas of nano- and materials science, for example for better lithium-ion batteries.”

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