Biomechanical Regulation of Microbial Self-Organization in Confined Environments

受限环境中微生物自组织的生物力学调控 在宿主体内，微生物在空间限制下生长，经常变得如此拥挤，以至于机械地 压力会影响他们的行为。例如，在人类体内，微生物通常会形成结构精细的聚集体 在牙齿的空洞、皮肤毛囊或结肠的隐窝状结构中，这越来越被认为是一种 影响人类健康的重要因素。尽管集体微生物的新一层机械调节 近年来出现了增长和运动，但我们对这种监管如何影响自我知之甚少。 微生物群落的组织。主要的挑战是从实验上监测和从理论上 同时对力量和增长之间的反馈进行建模，并跨越多个规模。 拟议研究的目标是量化和建模增长之间的直接和间接反馈。 和机械力，以解释和预测密集细胞群体的自组织。 为此，P.I.提出了从细胞到社区层面的微流控和谱系追踪实验 规模，以及外推模拟和理论。这项拟议的研究利用了激烈的对话 在他的实验室里培养的理论和实验之间，实现对自我的预测性理解 微生物种群中单个细胞联合作用下的组织。 私家侦探有两个明确的目标。首先，他将识别和描述生理适应，以使 微生物种群能够承受较大的机械应力和细胞形状变形。了解以下内容 力和生长之间的直接反馈将阐明力在寄主病原体入侵中的作用， 这是致死性的关键一步。其次，他将阐明致密的微生物种群是如何在 微环境，他们如何抵御入侵者，翻身和适应。回答这些问题会让你知道 在肠道或其他拥挤环境中促进或扰乱具有弹性的微生物生态系统的策略。 拟议中的工作开发了最先进的微流控技术，使时空自动化成为可能 细胞跟踪和在定义的机械边界下跟踪进化过程的新策略 条件。发展的模拟综合了现代种群遗传理论和特征丰富的生物物理 模拟和弥合实验室实验和自然实验在时空尺度上的差距 人口。计划中的新型微流控装置和计算机模拟将对 生物物理学社区，目标是解剖微生物种群的集体属性。 1

Title: Biomechanical regulation of microbial self-organization in confined environments Inside hosts, microbes grow under spatial constraints and frequently become so crowded that mechanical stresses influence their behavior. For example, within humans, microbes often form fine-structured aggregates in cavities on teeth, skin follicles, or crypt-like structures in the colon, which are increasingly recognized as an important factor influencing human health. Although new layers of mechanical regulation of collective microbial growth and motion have emerged in recent years, we know little about how such regulation influences the self- organization of microbial communities. The main challenges are to experimentally monitor and theoretically model the feedback between forces and growth at the same time and across multiple scales. The objective of the proposed research is to quantify and model the direct and indirect feedback between growth and mechanical forces in order to explain and predict the self-organization of dense cellular populations. To this end, the P.I. proposes microfluidic and lineage tracking experiments spanning cellular to community-level scales, as well as extrapolating simulations and theory. The proposed research leverages the intense dialog between theory and experiment cultivated in his laboratory to achieve a predictive understanding of self- organization in microbial populations in terms of the joint actions of individual cells. The P.I. has two specific aims. First, he will identify and characterize physiological adaptations that enable microbial populations to sustain large mechanical stresses and cell shape deformations. Understanding such direct feedback between forces and growth will illuminate the role of forces in the pathogenic invasion of hosts, which is a key step for virulence. Second, he will elucidate how dense microbial populations establish in tight micro-environments, how they fend off invaders, turn over and adapt. Answering these questions will inform strategies to promote or perturb a resilient microbial ecosystem in the gut or other crowded environments. The proposed work develops state-of-the-art microfluidic techniques that enable automated spatio-temporal tracking of cells and a novel strategy to track evolutionary processes, under defined mechanical boundary conditions. The simulations developed synthesize modern population genetic theory with feature-rich biophysical simulations and bridge the gap in spatio-temporal scales between laboratory experiments and natural populations. The planned novel microfluidic devices and computer simulations will be of broad utility to the biophysics community for the goal of dissecting collective properties of microbial populations. 1