Biomechanical Regulation of Microbial Self-Organization in Confined Environments

题目：密闭环境中微生物自组织的生物力学调节 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 压力会影响他们的行为。例如，在人体内，微生物经常形成精细结构的聚集体 在牙齿上的空腔、皮肤毛囊或结肠中的隐窝样结构中，这些结构越来越被认为是 影响人类健康的重要因素。虽然新的机械调节层的集体微生物 生长和运动是近年来出现的，我们对这种调节如何影响自我知之甚少， 微生物群落的组织。主要的挑战是实验监测和理论上 同时在多个尺度上模拟力量和增长之间的反馈。 本研究的目的是量化和模拟增长之间的直接和间接反馈， 和机械力来解释和预测致密细胞群的自组织。 为此，PI提出了微流体和谱系跟踪实验，从细胞到社区水平， 规模，以及推断模拟和理论。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，以实现对自我的预测性理解， 微生物种群中单个细胞的联合作用。 私家侦探有两个具体目标。首先，他将识别和描述生理适应， 微生物种群以承受大的机械应力和细胞形状变形。理解这些 力和生长之间的直接反馈将阐明力在病原体入侵宿主中的作用， 这是毒性的关键步骤。其次，他将阐明密集的微生物种群是如何在紧密的环境中建立起来的。 微环境，它们如何抵御入侵者，翻转和适应。回答这些问题将有助于 促进或扰乱肠道或其他拥挤环境中弹性微生物生态系统的策略。 拟议的工作开发了最先进的微流体技术，使自动时空 在限定的机械边界下，跟踪细胞和跟踪进化过程的新策略 条件开发的模拟综合了现代种群遗传理论与功能丰富的生物物理 模拟并弥合实验室实验与自然实验之间时空尺度上的差距 人口。计划中的新型微流体装置和计算机模拟将对微流体领域具有广泛的实用性。 生物物理学社区的目标是解剖微生物种群的集体性质。 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