Chief Scientist: Prof. Zhong-Can Ou-Yang

Participants in ITP: Chen Xiao-Song,Zhou Hai-Jun and some students

Main Research Topic:

The joint project "Research on the construction, working mechanism and potential application of biological nanomachines" is under the grant of National Basic Research Program of China (973 Program) which is initiated by the Ministry of Science and Technology of the People's Republic of China. This joint project consists of the following four sub-projects (four different research groups), supporting the extensive investigation (either experimentally or theoretically) on the construction, driving, optimization and application of two special biomolecular machines, the protein motor F0F1-ATP sythase and the single-stranded nucleic acid device i-motif. The ultimate goal of this project is to get better understanding of the design and optimization principle of soft-matter nanomachines driven by chemical reactions.

Sub-project I:  study on the structure and kinetics of FOF1-ATP synthase and its derivatives, by Group I of Prof. Jiachang Yue from Institute of Biophysics, CAS. They can modify FOF1-ATP synthase in various genetic ways to construct different rotors on liposomes or cell membranes, power the rotors by hydrogen concentration jump cross the membrane, and monitor the rotating speed by fluorophore which is ultra-sensetive to the hydrogen concentration outside the liposome. Different construction of rotor can lead to different rotation kinetics, which sheds some light on the optimization of rotor performance. Potential applications of these nano-rotors are being explored.

Sub-project II:  study on the self-assembly mechanism and control strategies of nano-actuator i-motif, by Group II of Prof.Dongsheng Liu from Department of Chemistry of Tsinghua University. The single-stranded nucleic acid i-motif can self-assemble into a very compact structure under low pH value and change to random-coil conformation by increasing the pH value, which leads to a large-scale actuation if one end of i-motif is immobilized. Variety of robust and controllable ways to tune the pH value (e.g., light-induction) have been established, which can serve as stable energy input to power the device working for numerous circles. The potential application of actuating device is being explored by sub-project IV. Single molecule experiments (e.g., AFM or magnetic tweezer) on i-motif are also ongoing to quantitatively evaluate the performance of this nano-actuator.

Sub-project III:  theoretical invesitation on the kinetics and non-equilibrium thermodynamics of biological nanomachines, by Group III of Prof.Zhong-can Ou-yang from Institute of Theoretical Physics, CAS. Both protein nanomachines like ATP synthase and nucleic acid nanadevice like i-motif, are good examples of soft-matter nanomachines which can convert chemical energy into mechanical work. Although the working principle of such nanomachines can be understood by physical models like Brownian ratchet, details of how chemical energy is used remains unsolved. Coarse-graining models relating the molecular structure of biological nanomachines to their kinetics and thermodynamics are under development in this group, and energetic performance of nanomachines are especially discussed. Other theoretical studies like single-molecule experimental data analysis and modeling are also part of the sub-project.

Sub-project IV: exploration on the potential application of biological nanomachines in medical sciences, by Group IV of Prof.Qinhua Fan from  Institute of Chemistry, CAS. Collaborated with Group I and II, they modify FOF1-ATP synthase or i-motif to design new nanomachines to meet some medical porposes.  For instance, adding antibody on the modified FOF1-ATP synthase (rotor) have been succesfully applied to high-resolution and low-dosage detection of some kinds of virus by monitoring the sudden change of the rotating speed when the virus binds onto the antibody. When i-motif is covalently linked to two half-sphere-like dentrimer, light-driven i-motif actuation can make the whole dentrimer sphere close or open, which can hopefully be used as a controllable and smart way for drug delivery and release.