Biomechanical Regulation of Microbial Self-Organization in Confined Environments

密闭环境中微生物自组织的生物力学调节

• 批准号: 10445778
• 负责人: Oskar Hallatschek
• 金额: $ 32.58万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10445778
• 关键词: Address; Bacteria; Behavior; Biological Assay; Biological Models; Biomechanics; Biophysics; Bone Tissue; Candida albicans; Cell Cycle Progression; Cell Proliferation; Cell Shape; Cell Wall; Cell model; Cells; Colon; Communities; Complement; Computer Simulation; Confined Spaces; Crowding; Data; Dental; Dental Implants; Disease; Drug Costs; Drug resistance; Ecosystem; Engineering; Environment; Environmental Impact; Epithelial Cells; Escherichia coli; Evolution; Feedback; Funding; Generations; Genetic; Genetic Variation; Genetic study; Goals; Growth; Habitats; Health; Homologous Gene; Human; Individual; Invaded; Joints; Laboratories; Laws; Liquid substance; Measures; Mechanical Stress; Mechanics; Medical; Microbe; Microfluidic Microchips; Microfluidics; Modeling; Modernization; Monitor; Motion; Mutagenesis; Organism; Outcome; Pathogenicity; Physiological; Physiological Adaptation; Population; Population Dynamics; Population Genetics; Population Growth; Process; Property; Regulation; Research; Role; Saccharomyces cerevisiae; Saccharomycetales; Shapes; Skin; Structure; System; Techniques; Testing; Theoretical model; Time; Tissues; Tooth structure; Urinary tract; Urinary tract infection; Virulence; Work; Yeasts; base; biological adaptation to stress; cell growth; colonization resistance; commensal microbes; experimental study; fungus; gene network; gut microbiome; improved; insight; intestinal crypt; laboratory experiment; mathematical model; mechanical force; microbial; microbial community; microbiome; mutant; novel; novel strategies; opportunistic pathogen; pathogen; pathogenic fungus; pathogenic microbe; pressure; resilience; resistance mutation; self organization; simulation; soft tissue; spatiotemporal; theories

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

标题：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，并且经常变得非常拥挤，以至于机械 压力影响他们的行为。例如，在人类体内，微生物通常形成精细结构的聚集体 在牙齿、皮肤毛囊或结肠隐窝样结构的空洞中，这些结构越来越被认为是一种 影响人体健康的重要因素。尽管集体微生物的机械调节新层 近年来出现了生长和运动，但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。主要挑战是实验监测和理论上 同时跨多个尺度对力量和增长之间的反馈进行建模。 拟议研究的目的是对增长之间的直接和间接反馈进行量化和建模 和机械力，以解释和预测密集细胞群的自组织。 为此，P.I.提出了从细胞到群落水平的微流体和谱系追踪实验 尺度，以及推断模拟和理论。拟议的研究利用了激烈的对话 实验室培养的理论与实验之间的联系，以实现对自我的预测性理解 根据单个细胞的联合行动来组织微生物群体。 P.I.有两个具体目标。首先，他将识别并描述生理适应，使 微生物种群能够承受巨大的机械应力和细胞形状变形。了解这样的 力与生长之间的直接反馈将阐明力在宿主病原体入侵中的作用， 这是毒力的关键一步。其次，他将阐明微生物种群如何在紧密的环境中建立起来。 微环境，它们如何抵御入侵者、翻转和适应。回答这些问题将告知 促进或扰乱肠道或其他拥挤环境中具有弹性的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，能够实现自动化时空 在定义的机械边界下跟踪细胞和跟踪进化过程的新策略 状况。开发的模拟综合了现代群体遗传理论和特征丰富的生物物理学 模拟并弥合实验室实验和自然实验之间时空尺度的差距 人口。计划中的新型微流体装置和计算机模拟将具有广泛的用途 生物物理学界的目标是剖析微生物种群的集体特性。 1