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New Nanospheres Measure the Tiny Forces of Biological Motors

Motor proteins produce the forces required for crucial mechanical processes in the human body. On a nanometer scale—that is, a millionth of a millimeter—motor proteins, for instance, transport material within the human cells, or power the human muscles.

Kinesin motor transports vesicle along microtubule.

Kinesin motor transports vesicle along a microtubule. Video Credit: University of Tübingen.

Invisible to the naked eye, these movements can be made perceptible by Erik Schäffer, a professor of Cellular Nanoscience from the University of Tübingen. He designs unique force microscopes, the so-called optical tweezers, to quantify the way these molecular machines operate mechanically.

Professor Schäffer’s research team, from the Center for Plant Molecular Biology, has now further enhanced this technology. Unique probes, such as germanium nanospheres, allow a higher resolution of forces and displacements generated by the motors. The results of the study have been published in the Science journal.

The motor proteins, which have been extensively studied and measuring only 60 nm in size, are actually very small but are nevertheless crucial for cellular processes. Among other things, these proteins help to mechanically separate chromosomes at the time of cell division, or they transmit tiny 'packages,' the so-called vesicles, inside the cells.

For instance, dysfunctional motors in nerve cells may cause neurological disorders, including Alzheimer’s disease.

To reveal the functions of motor proteins, biophysicist Erik Schäffer has designed optical tweezers that are highly precise. These optical tweezers are based on principles that were previously identified by astronomer Johannes Kepler in 1609, and this invention fetched the 2018 Nobel Prize for the physicist Arthur Ashkin.

The ultra-precise optical tweezers manipulate the radiation pressure of laser light to hold the minute particles in place without making any contact.

With the help of this tool, Professor Schäffer was able to demonstrate several years ago that the motor protein, called kinesin, revolves while walking—with a pair of 'feet,' it takes eight-nanometer large steps and makes a half-turn every time—almost as if doing the Viennese waltz.

Swathi Sudhakar, a PhD student of Professor Schäffer, has now further improved the optical tweezers technology. Using germanium nanospheres, which are higher resolution and relatively smaller probes, the inconceivably small, five-piconewton forces of the biological motors can still be counteracted.

This means that the investigators can now quantify even the fastest and smallest movements that were, until now, concealed in the storm of the jerky thermal movement intrinsic to tiny particles.

Using the novel technology, the team could monitor the kinesin in real time, and Sudhakar identified yet another intermediate step in its locomotion, rendering the waltz nearly perfect.

Whether this intermediate step exists has been debated among scientists for 20 years. We were able to measure this directly for the first time using optical tweezers.

Erik Schäffer, Professor of Cellular Nanoscience, the University of Tübingen

The nanospheres also showed a formerly unfamiliar slip mechanism of the motor.

It is a kind of safety leash that keeps the motor on track if the load is too high,” Schäffer added. This kind of mechanism describes the excellent efficiency of vesicle transport within the cells.

If we know how kinesin motors work in detail, we can also better understand the vital cell processes that the motors power, as well as malfunctions that can lead to disease.

Erik Schäffer, Professor of Cellular Nanoscience, the University of Tübingen

Professor Schäffer compared the novel technology with “taking a good look under the hood” of molecular machines. According to him, researchers can now accurately visualize individual motions of molecular machines and can also gain a better understanding of, for instance, how proteins fold into their precise structure.

As semiconductors, the nanospheres have additional exciting optical and electrical properties. Therefore, they could be useful in other areas of nanoscience and materials science, for example, for better lithium-ion batteries.

Erik Schäffer, Professor of Cellular Nanoscience, the University of Tübingen

Journal Reference

Sudhakar, S., et al. (2021) Germanium nanospheres for ultraresolution picotensiometry of kinesin motors. Science.

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