Multiscale Studies of Collective Behavior in a Model Social Bacterium

从角马群到细菌生物膜，以及两者之间的每一个尺度，个体如何自组装成大的、空间复杂的群体是理解集体行为、多细胞和发育的关键问题。个体在细胞水平上的协调运动可以驱动组织、生物体和群体中更高尺度结构的形成。这些现象在统计上是由于细胞根据局部和全局信号调节其方向和速度而产生的。充分理解细胞群体中的集体行为是如何产生的很难实现，因为社区目前缺乏物理探测感觉输入，运动控制和群体形成的方法。研究特定突变对单细胞运动和群体形态影响的实验已经确定了许多重要的分子参与者，但缺乏探测群体内个体行为或运动产生和协调的物理方面的能力。虽然目前大多数移动细菌群体的模型严重依赖于细胞之间的机械耦合作为集体行为的关键驱动因素，但在这种情况下，我们几乎没有测量力对细胞运动或方向性的影响。在这个项目中，PI将研究生物物理方面的力量产生，运动控制，以及细胞-细胞协调在分子到多细胞水平上使用模式社会细菌粘球菌黄。这项工作的三个目标是确定物理力量在协调细胞速度和方向性方面的作用，并阐明驱动基于饥饿的聚集的单细胞运动的特性。即将进行的实验将使我们对单个细胞如何运动以及它们如何协调它们的活动以形成大规模的、可运动的结构的理解产生巨大的飞跃。该项目通过使用物理测量和分析来了解活细胞在空间尺度上的动力学，牢牢地符合美国国家科学基金会生命系统物理学计划的目标。PI已经开发了一门跨学科的综合科学课程，并将在未来几年改进课程的课程设置，使其更容易为更多的美国大学生所接受，一旦完成，将率先出版一本教科书以供广泛传播。此外，作为本提案的一部分开发的许多技术和分析将服务于更大的微生物群落，并将免费提供。该项目由物理系的生命系统物理学项目和分子与细胞生物科学系的细胞动力学和功能项目共同支持。

From wildebeest herds to bacterial biofilms and every scale in between, how individuals self-assemble into large, spatially complex groups is a key problem in understanding collective behavior, multicellularity and development. The coordinated motion of individuals at the cellular level can drive the formation of higher-scale structure in tissues, organisms and populations. These phenomena arise statistically as cells modulate their direction and speed in response to both local and global cues. A full understanding of how collective behavior in cell populations arises has been difficult to achieve because the community currently lacks methods to physically probe sensory input, motor control, and group formation. Experiments examining the effect of specific mutations on single cell movement and group morphology have identified many important molecular players but lack the ability to probe the behavior of individuals within groups or physical aspects of motion production and coordination. While most current models of motile bacterial populations rely heavily on mechanical coupling between cells as a key driver of collective behavior, we have virtually no measurements of the effect of forces on cell movement or directionality in this context. In this project the PI will study biophysical aspects of force production, motion control, and cell-cell coordination on the molecular to the multi-cellular level using the model social bacterium Myxococcus xanthus. The three aims of the work seek to determine the role of physical forces in coordinating cell speed and directionality and to elucidate the properties of single-cell motility that drive starvation-based aggregation. The experiments that will be performed will generate a huge leap forward in our understanding of how individual cells move and how they coordinate their activities to form large scale, motile structures. This project lies firmly within the goals of the Physics of Living Systems program at the NSF by using physical measurements and analyses to understand the dynamics of living cells across spatial scales. The PI has developed a cross-disciplinary Integrated Science course and will use the next several years to improve the course's curriculum by making it more accessible to a larger audience of US college students and, once complete, spearhead efforts to publish a textbook for broad dissemination. In addition, many of the techniques and analyses developed as part of this proposal will serve the larger microbiological community and will be made freely available.This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Cellular Dynamics and Function Program in the Division of Molecular and Cellular Biosciences.