多物理场对大肠杆菌微生物膜（Biofilm）形成的影响

Biofilm is responsible for more than 80% of microbial infection in human body. It also causes huge loss in industry and everyday life. It is a gathering of microorganism cells which are bounded by extracellular polymeric substances (EPS) in wet environment and can develop quickly under complicated mechanical, physical and chemical conditions. The controlling factors and mechanism of this fast developing process need to be explored by methods which combine biological, mechanical and physical tools. The model bacteria and the most understood microorganism, E. coli, is used in this research for biofilm formation. This is possible after a novel method was recently found in our previous work to increase the biofilm production rate by at least 2 magnitudes, comparing to the traditional ways. The biofilm formation process consists of three "phases" of cells: free swimming, small clusters, and the immobile biofilm. This proposed work combines experimental methods in biophysics and biomechanics to monitors the characteristics of this process, in order to obtain its "phase diagram". We propose to explore the biofilm formation mechanism by applying analytical models in soft condense matter physics. The results will provide scientific support for controlling/suppressing the growth of biofilm and a safe replacement for the traditional, antibiotic abused treatment.

微生物膜（Biofilm）是大量微生物细胞在湿润环境中紧密结合的生存状态，超过80%的微生物感染与微生物膜（Biofilm）有关，并在工业和日常生活中造成水管拥堵、仪表腐蚀等大量损失。而外界环境的温度、湿度、流场、营养、乃至微生物入侵部位的微观构造等物理、化学因素都可能对微生物膜的形成和扩展产生显著影响，这需要综合采用生物、力学、及物理等学科的方法，来研究控制微生物膜形成生长的决定性参数和机理。本研究将针对大肠杆菌（E. coli），结合囊泡微流体生成技术，研究多物理场下大肠杆菌微生物膜的形成，采用生物物理及生物力学的定量测量方法，实时监控该过程的系统特征参数，辅以流体力学及软物质研究的理论模型分析，系统地研究导致微生物膜迅速生成及扩展的生物物理机制。由于所采用的细菌模型及环境因素有普遍代表性，本研究结果可以为有效控制微生物膜生长提供科学依据。

生物被膜（Biofilm）由于在医药健康、生产生活等领域的重要影响，以及涉及细菌的群体及个体运动特性、趋化行为、对环境的响应等科学问题，一直是生命科学、生物物理、生物力学等交叉领域的研究热点。本研究1）构建了基于玻璃毛细管的微流体设备，用以植入细菌并生成生物被膜；2）与尼康公司合作搭建了温度控制平台，得以实现环境变化下定量测量生物被膜的生成速度；3）定量研究细菌在形成微生物膜前，其运动能力、细胞体特征等生命体本身因素的改变如何影响微生物膜的形成；4） 研究了马达运动特性在高密度下对环境的响应；5）测量了生长条件对细菌趋化性能的影响；6）研究了鞭毛马达动力学的定量测量及别构调控机制。在本项目执行期间，共发表SCI论文4篇，包括Nature Physics 1篇，Biophysical Journal 1篇，PNAS 1篇，Phys. Rev. E 1篇。其它一些重要结果也准备投稿。