Previous Results

I have been focusing on the unique properties of nature's nano machine using motor protein (myosin) as a model system.

 Motor protein is a 10-nm size molecule and achives force generation or directional motion under Brownian noise which is inevitable in the nano world. Input energy to drive motor protein is supplied from ATP (Adenosine Triphosphate) molecules. Although man-made system such as semiconductor devices uses huge amount of input energy (108 kBT/bit) to completely shut down the Brownian noise, motor protein cannot shut down the noise due to the low input energy of ATP (20kBT). Therefore, these nanomachine must deal with the noise in a different manner compared with man-made system and achieve physiological function.

 There would exists various logic to get along with thermal noise and stochastic behaviours at each biological hierachy, but I have been approaching the issue at the molecular level by refining the single molecule measurement techniques (optical tweezers, single molecule imaging)

  My notable results are as follows.

1. Strain sensor mechanism of myosin as a rectification of random Brownian motion

Detail is linked here but briefly, I focused on the essential point of force generation mechanism, that is, How to determine the directionality? or What's the symmetry breaking mechanism?  We found that strain-sensing mechanism in the motor domain rectified the random Brownian motion, resulting in a directional motion along actin tracks. The phenomenon is apparrently similar with Maxwell's demon in that work is produced from random motion. Therefore, strain sensor acts as a demon. Although the strain-sensing is coupled with the chemical cycle of ATP hydrolysis (Pi release), which means the mechanism doesn't violate thermodynamic low, we clarified the biological molecular motors called myosin-V and VI are Brownian molecular machine. The input energy of ATP is consumed by keeping the motor in the forward.

2.Quantification of elementary mechanical process by a mechanical control of Brownian process

Detail is linked here. Briefly, we found swiching of force genration mode of myosin-V depending on external load. Mainly, two mechanical processes are important for the motor function, one is structural change termed "Lever-arm swing" and the other is rectification of Brownian motion we termed "Brownian search-and-catch".  Lever-arm swing is well-known mechanism and written in the popular biology text as a muscle contraction mechanism. Recent single molecule measurements revealed the lever-arm swing but there were less imformation about energetics (actual measurement data). That is,

 How large is the contribution of structural change of lever-arm swing ?

 How large is the contribution of Brownian search-and-catch?

 We solved the question by constructing single molecule techniques and DNA molecules as a nano material.

 In summary, Lever arm swing contributes by 15 % of whole work near stall condition. Remainings are driven by the Brownian search-and-catch. We quantified the output work using myosin-V but the distribution of these contribution may be different between myosin molecules (over 30 kinds of myosins exists).

 Notable finding here is not only renewing the textbook but stochastic process such as Brownian search-and-catch playes a critical role in the function and indicating a very wise nature when we imagine motor function in a cell environment. That is, myosin-V functions as a delivery machine to transport vesicles in a cell. Unlike railway track or turnpike, myosin-V moves along cytoskeletal actin filament where various obstacles such as binding proteins (filamin etc.) exists. In addition, cytosol is very crowded, so, myosin-V must avoid many obstacles in a cell. Because the Brownian search-and-catch is a Brownian process, motor can diffuse between obstacles and search and find appropriate landing position. Therefore, we believe myosin-V can robustly and adaptably transport vesicles in a cell.

 Nature's nano machine is designed such that inevitable process by structural change and highly stochastic process by Brownian search-and-catch are hybridized to function efficiently in a cell.

3.Motor function and water dynamics toward understanding the energy of ATP

We have challenged to construct the model of motor function where water dynamics is explicitly incorporated in the model. please see Grant-in-Aid for Scientific Research on Innovative Areas 「Water and energy of ATP.   

  In summary, I propose multiple regulation mechanism for the motor function depending on the environmental factor. By responding to environmental parameters such as force field, osmotic pressure and  crowding effect predicted in a cell, force generation mechanism is switched to adapt to surroundings. Motor proteins have evolved to robustly achive the function by adapting the surroundings.