Nature is inherently stochastic. Yet, many natural processes seem to be precisely coordinated. How do biological systems achieve such a high level of precision? Researchers at the B CUBE – Center for Molecular Bioengineering and the Cluster of Excellence Physics of Life (PoL) have experimentally demonstrated how thousands of independently operating molecular motors synchronize to generate regular, coordinated beating of the axoneme, the internal mechanical core that powers motile cilia such as the sperm tail. Their study provides insights into how biological systems harness collective dynamics to achieve precision. The findings were published in the "Proceedings of the National Academy of Sciences”.
Sperm cells are tiny, efficient swimmers. They use their whip-like tails to move through the liquid. These tails are powered by thousands of molecular motors that must work in unison to achieve highly regular movement. But how do these tiny motors, each acting independently, coordinate to create a synchronized and powerful movement? TU Dresden researchers, Dr. Veikko Geyer (Diez group, B CUBE) and Prof. Benjamin Friedrich (PoL) combined their expertise to tackle this question.
Understanding the Noisy Beat of Axonemes
“The molecular motors responsible for the beating of cilia – like the sperm tail - are arranged in a special structure made of microtubules, known as the axoneme,” explains Dr. Geyer. “The axoneme’s architecture is evolutionarily conserved across species, from single-celled organisms to humans. This makes it possible for us to study axonemes in simpler organisms, like green algae, to understand cellular motility principles relevant to human biology.”
Using super high-speed microscopy capable of capturing 1,000 images per second, the team precisely measured the fluctuations in the beat of reactivated axonemes, isolated from the green alga Chlamydomonas reinhardtii. ‘’This cell-free model system allows us to study the noise that is purely generated by the molecular motors in the mechanical system,” says Dr. Geyer.
The Power of Collective Action
“Mathematical modeling allows us to simulate the collective dynamics of many molecular motors acting together and make predictions,” says Prof. Friedrich. The models prepared by Prof. Friedrich predicted that the noise of the system should depend on the number of molecular motors. As the number of active motors increased, the noise would decrease, and the tail’s beating would become more regular.
To test this, the team developed an experimental assay to reduce the number of active motors within an axoneme and observe the effects on beating. Their experimental results confirmed the theoretical predictions. More motors led to better coordination and reduced noise. “The collective activity of many motors together increased the precision of the beat,” says Dr. Geyer.
Molecular Pacemakers in Action
The axoneme generally contains two types of motors: those positioned on the outer edge of the structure and those inclined towards the inside. “We developed a method to gradually remove either the inner or the outer motors,” says Dr. Geyer. When the inner motors were removed, the disturbance to the axoneme beating was much greater than when the outer motors were removed, suggesting a special role for the inner motors.
“We hypothesize that the inner motors work as pacemakers and synchronize the action of the other, more abundant, outer motors. This, together with the reduction of noise through the collective work, boosts the regularity of the beat,” concludes Prof. Friedrich.
Empowering the Next Generation of Scientists
A young scientist from India, Abhimanyu Sharma, made significant contributions to this study. As a visiting Master’s student at TU Dresden, he was supported by funding from the Dresden International Graduate School for Biomedicine and Bioengineering (DIGS-BB) and the German Academic Exchange Service (DAAD).
"Abhimanyu's dedication was instrumental in driving this project forward," says Dr. Geyer. "His work highlights the importance of international collaboration and the potential of young researchers to make significant contributions to science."
After completing his Master’s at the Indian Institute of Science Education and Research in Mohali, India, Abhimanyu is now pursuing his Ph.D. at Stanford University, USA, continuing his scientific journey.
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Original Publication
Abhimanyu Sharma, Benjamin M. Friedrich, and Veikko F. Geyer: Active fluctuations of axoneme oscillations scale with number of dynein motors. PNAS (November 2024)
Link: https://doi.org/10.1073/pnas.2406244121
Scientific Contacts:
Dr. Veikko F. Geyer
E-Mail: veikko.geyer@tu-dresden.de
Prof. Benjamin M. Friedrich
E-Mail: benjamin.m.friedrich@tu-dresden.de