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Elucidation of geometric laws that govern the swarm motion of biomolecular motors
Living organisms such as birds, fish, bacteria, etc. move autonomously and gather in large numbers to form flocks that exhibit collective motion. Cytoskeletal filaments that are propelled by biomolecular motors form groups in plant cells and are thought to play an important role in controlling cell shape. However, the associated traffic rules for molecular swarming which is inevitable to manipulate the swarm movement of cytoskeletal filaments and to create ordered structures or patterns have not been clarified. I, with my colleagues, have discovered a geometric rule for traffic control of a group of cytoskeletal proteins driven by a biomolecular motor. We also used this rule to fabricate a cytoskeletal structure that is found in cells. The findings obtained in our study are expected to clarify the basic rules for manipulating group behavior of molecules and lead to the development of innovative devices that run on the chemical energy of biomolecular motors.
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The first evidence of mechanosensitive behavior of microtubules
Microtubule is the most rigid component of eukaryotic cytoskeleton which plays pivotal roles in many cellular functions. Role of microtubules in cellular mechano-transduction and mechano-regulation of cellular activities has been long suspected. Our research team, led by Associate Professor Akira Kakugo of Hokkaido University, has provided direct evidence that microtubules function as mechanosensors and regulate intracellular transport. The team included Dr. Syeda Rubaiya Nasrin, Seiji Nishikawa, Dr. Arif Md. Rashedul Kabir and Professor Kazuki Sada of Hokkaido University; Dr. Christian Ganser of the National Institutes of Natural Sciences; Associate Professor Takefumi Yamashita of Research Center for Advanced Science and Technology (RCAST), The University of Tokyo; Professor Mitsunori Ikeguchi of Yokohama City University; Professor Takayuki Uchihashi of Nagoya University; and Professor Henry Hess of Columbia University.
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Scientists working to make molecular robots to perform tasks
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Multi-disciplinary research has led to the innovative fabrication of molecule-sized robots. Scientists are now advancing their efforts to make these robots interact and work together in the millions, explains a review in the journal Science and Technology of Advanced Materials. The lead author Dr. Kabir, with his colleagues, contributed in developing molecular robots using three key components: microtubules, single-stranded DNA, and a light-sensing chemical compound. The microtubules act as the molecular robot's motor, by converting chemical energy into mechanical work. The DNA strands act as the information processor due to their incredible ability to store data and perform multiple functions simultaneously. The chemical compound, azobenzene derivative, is able to sense light, acting as the molecular robot's on/off switch. Issues related to energy efficiency and reusability, in addition to improving the lifetime of molecular robots, still need to be addressed in future.
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In recent years, reconstructed biomolecular motors have appeared as promising substitutes of synthetic motors and expected to be key components in biomimetic artificial micro- or nano-devices. However, reconstructed biomolecular motors lose their ability to function due to thermal instability in artificial environments. Tasrina Munmun, Dr. Arif Md. Rashedul Kabir, Dr. Kazuki Sada and Dr. Akira Kakugo of Hokkaido University and Dr. Yukiteru Katsumoto of Fukuoka University were inspired by seeing how proteins remain stable in living organisms such as sharks, teleosts, skates, and crabs that survive in harsh environments like deep sea hydrothermal vents or under thermal perturbations. They noticed that the proteins in deep-sea animals remain stable and active thanks to trimethyamine N-oxide (TMAO). The team discovered a method to control the activity of biomolecular machines over a wide temperature range using the deep-sea osmolyte trimethylamine N-oxide (TMAO). This finding could open a new dimension in the application of artificial machines fabricated from biomolecular motors and other proteins.
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Microtubules are cylindrical proteins that work as the train tracks for motor proteins and allow transportation of molecular cargos in cells. Traumatic brain injuries are believed to be linked to deformation of microtubules under mechanical force or impact, and consequent malfunction of the motor driven transportation along microtubules. Dr. Arif Md. Rashedul Kabir and his colleagues at Hokkaido University has developed a technique to investigate how mechanical deformation of the tiny train track-like cell proteins affects their function in molecular transportation. The findings could help clarify the roles of deformed microtubules in traumatic brain injuries and various neurological diseases.
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The fusion of DNA nanotechnology and biomolecular motors has been useful in successfully realizing the dynamic contraction of giant microtubule protein networks, like the smooth muscles in living organisms. The dynamic contraction only happened in the presence of a DNA origami, that facilitated hierarchical self-assembly of microtubule filaments. Further studies could lead to the use of DNA for controlled, programmable self-assembly and contraction of biomolecular motor systems. Such motors could find applications in molecular robotics and the development of micro/nanodevices for nanotechnological applications.
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Molecular robots were fabricated by utilizing biomolecular motors and DNA that autonomously exhibited swarming in response to chemical and physical signals. Reconstructed cellular proteins called microtubules and kinesins were used as the actuator, and DNA was used as the information processor for the molecular robots. The energy required to drive the robots was obtained from the hydrolysis of adenosine triphosphate (ATP). Azobenzene, a photoresponsive molecule, was utilized as the sensor for the robots. The sensor permitted photo-irradiation-induced switching between the solitary and swarm state of the robots. The swarms of robots can also move with translational or rotational motion depending on their rigidity.
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In a novel strategy, tiny “Walking” protein molecules have been used to characterize the surface mechanical deformations in soft materials. Filament-shaped proteins, such as microtubules, are driven by two foot-shaped protein kinesin. these walking proteins and their associated proteins are used as sensors for detecting tension and compression in the soft silicon-based material polydimethylsiloxane (PDMS). Since deformation of the soft materials mimics the environments of living cells, this work could also help make clear the functions and mechanisms of motor proteins and microtubules in cells.