多尺度细胞模拟理论和算法研究

Huge challenge has been presented to the modern multi-scale scientific research due to the time-space multiple matrix features of life behaviors. Up-to-date, a well-rounded multi-scale theory or model for precisely reflection of the cooperation and interaction mechanism of the coupled micro- and macroscopic behaviors of cellular system is still unavailable. With the help of statistical mechanics and dynamics, this project is devoted to develop an integrated multi-scale framework theory and algorithm that is applicable to multiple-layer biological systems ranging from the intracellular macromolecules, sub-cellular system, cell to the tissue levels, and thus to in theory and practice study the cell communication, directional motility as well as the tissue formation mechanisms. Meanwhile, the developed theory is also used to model several typical multi-scale behaviors including the Wnt-β catenin-cadherin pathway, the integrin-Rac-JNK network, as well as the IgCAM pathway-mediated whole-cell adhesion, aggregation, and tumor cell metastasis and invasion mechanisms, and corresponding cell biology experiments for validation of the simulation results are also conducted. The successful launch of this project will establish a series of novel theories and algorithm tools for exploration of cell multi-scale physiological processes and provide basic support to the solution of multi-scale complex life systems.

生命行为的时-空多尺度特征给现代多尺度科学研究提出了巨大挑战。目前尚缺乏可以精确反映细胞微观-宏观行为交互耦合的多尺度理论和模型。本项目借助统计力学、统计动力学理论，开发一个统一框架下的适用于细胞内大分子、亚细胞、细胞到组织水平的时-空多尺度生命行为的模拟理论和算法，进而从理论上和实践上实现研究细胞通讯、细胞定向运动以及组织模型形成机制。同时，我们将该理论应用于Wnt-β catenin-cadherin通路、integrin-Rac-JNK网络，以及IgCAM通路所介导的细胞黏附、团聚、以及肿瘤细胞转移和入侵机制等典型多尺度行为的研究，并开展细胞生物学实验验证。本项目的成功开展将建立一套研究细胞多尺度生理过程的新理论和新工具，从而为解决复杂生命体系的多尺度问题提供基础性支持。

生命行为的时-空多尺度特征给现代多尺度科学研究提出了巨大挑战。目前尚缺乏可以精确反映细胞微观-宏观行为交互耦合的多尺度理论和模型。. 在该青年项目的支持下，我们成功开发了一套多尺度细胞模拟理论和算法，适用于细胞内大分子、亚细胞、细胞到组织水平的时-空多尺度生命行为的研究。该理论算法重点研究细胞通讯、细胞定向运动以及组织模型形成机制。在该理论和算法的基础上，我们成功开展了几个典型的细胞内生化通路、信号转导网络的模拟研究，主要包括p53蛋白调控机制的模拟分析，细胞分子间的相互作用机制和识别模式研究。同时在单分水平上，我们也尝试开展了生物大分子动力学模拟，小分子和蛋白质结合研究。. 该项目的实施已经取得了系列成果，目前共发表SCI论文20余篇，其中包括了Current Medicinal Chemistry, Soft Matter, RSC Advances，PLoS ONE 和Briefings in Bioinformatics等国际著名期刊，其中IF > 3.0 的论文7篇。该研究为解决复杂生命体系的多尺度问题提供基础性支持。