Single molecule analysis of chemotactic signaling system

点击翻译按钮获取中文摘要

(300 words)Chemotaxis, the process by which cells sense and respond directionally to chemical gradients, operates in a wide range of biological processes including immunity, neuronal patterning, and morphogenesis. How chemotactic cells reliably obtain information regarding the gradient from such noisy inputs is a critical question for directional sensing in chemotaxis.In this research, we have developed single molecule imaging techniques to monitor directly behaviors of individual bio-molecules in chemotactic signaling system. Single molecule imaging analysis of chemotactic response in eukaryotic cells revealed a stochastic nature in the input signals and the signal transduction processes. Also, we have developed a stochastic model of chemotactic signaling in which noise and signal propagation along transmembrane signaling by chemoattractant receptors can be analyzed quantitatively. The results obtained from these analysis reveal that the second messenger production reactions by the r … More eceptors generate noisy signals, which contain intrinsic noise inherently generated at this reaction and extrinsic noise propagated from the ligand-receptor-binding. Such intrinsic and extrinsic noises limit directional sensing ability of chemotactic cells which can explain the dependence of chemotactic accuracy on chemical gradients that have been observed experimentally. Our analysis also reveals regulatory mechanism for signal improvements in the stochastically-operating signaling system by analyzing how signal-to-noise ratio (SNR) of chemotactic singals can be improved or deteriorated by the stochastic properties of receptors and second messenger molecules.Our model provides a theoretical framework with experimental approaches to chemotactic signaling system and can further be applied to other stochastic signaling systems in general. Furthermore, inspired by biological processing, in which organisms manage successfully to acquire noise-robust characteristics and flexibility in their information processing, we proposed a stochastic calculation method based on the concept of stochastic computing. This will provide a complementary approach to technology based on conventional computing principles. Less