Imaging and nanomanipulation of single biomolecules at work: working principle of biological molecular machines

Summary form only given. The flexibility and efficiency of the biological molecular machines stands in sharp contrast to the situation of man-made machines, in which efficiency requires high-rigidity and high-energy inputs to overcome the interference of thermal noise. Biological machines operate without these requirements. In order to understand how biological molecular machines operate, we have developed new technologies that can detect movements of single biomolecules, single chemical reactions, and changes in conformation of single protein molecules in real time, and also manipulate single molecules in aqueous solution. These techniques have been applied to study a typical biomolecular machine, the molecular motor, in which the important functions of proteins, catalysis, energy transduction, molecular recognition, and self-assembly are integrated. We have directly observed motions, elementary mechanical events of nanometer-picoNewton level, conformational changes, and furthermore simultaneously observed individual ATPase and mechanical reactions of a single molecular motor. The results challenge the widely accepted models, which are based on an analogy to the manmade-machine, based on 0/1 logic and a high signal-to-noise ratio, and lead to a new conceptual framework for working principle of biological machines.