CAREER: Collective mechanics, particle transport and morphological adaptation in living multiphase matter: from mechanisms to the control of microbial swarms and films

该职业奖将支持一项综合研究和教育计划，以研究和模拟生命多相材料的形成和演化-微生物群和薄膜。细菌和真菌菌落构成了地球上生物量的很大一部分。这些微生物导致超过三分之二的人类疾病，包括大多数医院获得性感染。细菌和真菌通常通过形成快速扩散的多细胞群体和生长的纤维膜在表面和组织中定植。本研究的目的是了解这些形成的机制，并量化复合材料的涌现特性。所获得的知识可以启发新的技术来控制细菌和真菌感染在生理相关的设置。研究小组将研究微生物群和膜的形成、生长和适应性的基本物理和生化机制。该团队将使用粘质沙雷氏菌和大肠杆菌以及真菌白色念珠菌作为模型实验系统。实验数据将用于开发和测试分析理论和数值模型，以识别和理解所涉及的机制。在研究中获得的见解将在几个领域有用，包括组织工程，软物质，群体机器人和微生物学。该奖项还将通过设计基于拟议研究的干湿实验室组件的新课程来加强本科生和研究生的生物工程课程。受此研究启发，研究团队还将创建一系列可定制的、独立的和模块化的图形和可视化“SynLab”工具包和应用程序。这些将在K- 12教室实施，以激励学生从事STEM职业。该奖项将加强教育，促进社区指导外展，并为本科生和研究生提供研究机会，特别是那些来自代表性不足的群体的学生，包括加州中央山谷地区的美国印第安青年。细菌和真菌造成了超过三分之二的人类感染，它们是单独的，有时是共存的群落。在感染阶段，这些微生物通过形成快速扩散的多细胞群体和薄膜在物体表面定植。这些有生命的多相复合材料虽然由独立的主体（单位）组成，但却表现出大量的宏观特性，以及显著的集体反应和适应。我们对生物力学和物理化学机制如何启动、发展和稳定这种集体反应和复合特性的理解存在重大差距。该项目旨在通过综合研究、通识教育和社区参与外展计划来研究这些基本问题。本研究计划建立在以下基本假设之上：主动多尺度多相框架提供了一种新颖、完整和深刻的方法来询问、分析和理解微生物群和膜。PI和他的团队将把粘质沙雷氏菌、大肠杆菌和白色念珠菌的实验结合起来，运用多相连续体理论和基于随机代理的模拟来理解集体移动群体和快速生长的真菌膜中的集体力学、粒子运输和形态适应。具体目标是：1)询问和理解微观尺度的力学和运输，细胞-细胞相互作用和物理化学相互作用如何控制集体多细胞群体和膜的开始；2)跟踪这些复合材料中尺度时空特性和形态的演变，并量化其对外部流动、化学和机械扰动的适应；3)结合第一性原理连续统理论、最小模型和随机模拟，确定细菌/真菌微生物群落稳定性的物理机制；4)通过加入干湿实验内容，显著提升本科和研究生生物工程课程；5)受本研究启发，创建一系列基于独立应用程序的可定制模块化图形；6)为代表性不足的学生提供研究机会。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This CAREER award will support an integrated research and education plan to study and model the formation and evolution of living multiphase materials - microbial swarms and films. Bacterial and fungal colonies constitute a significant fraction of the biomass on earth. These organisms cause more than two-thirds of human disease including most hospital-acquired infections. Bacteria and fungi typically colonize surfaces and tissue by forming rapidly spreading multicellular swarms and growing fibrous films. The goal of this research is to understand the mechanisms by which these form and to quantifying emergent properties of the composite. The knowledge gained can inspire new technologies to control bacterial and fungal infections in physiologically relevant settings. The research team will investigate the fundamental physical and biochemical mechanisms that underlie formation, growth, and adaptability in microbial swarms and films. The team will use the bacteria Serratia marcescens and Escherichia coli, and the fungus Candida albicans as model experimental systems. Experimental data will be used to develop and test analytical theories and numerical models to identify and understand the mechanisms involved. Insights obtained in the research will be useful in several fields including tissue engineering, soft matter, swarm robotics, and microbiology. The award will also enhance undergraduate and graduate bioengineering curricula through the design of new courses with both wet and dry laboratory components based on the proposed research. The research team will also create a series of customizable, standalone and modular graphics and visualization heavy “SynLab” toolkits and applications inspired by this research. These will be implemented in K- 12 classrooms to motivate students toward STEM careers. The award will enhance education, contribute to community directed outreach, and provide research opportunities for undergraduate and graduate students, especially those from underrepresented groups, including American Indian youth in the Central Valley region of California. Bacteria and fungi cause more than two-thirds of human infections, separately and sometimes as coexisting communities. In the infectious phase, these microbes colonize surfaces by forming rapidly spreading multicellular swarms and films. These living multiphase composites, while composed of independent agents (units), exhibit bulk macroscale properties, and remarkable collective response and adaptations. There are significant gaps in our understanding of how biomechanical and physicochemical mechanisms initiate, develop and stabilize such collective response and composite properties. This project aims to study these fundamental questions through a comprehensive and integrated research, general education and community-engaged outreach program. The research plan builds on the following foundational hypothesis: active multi-scale multiphase frameworks provide a novel, complete and insightful means to interrogate, analyze and understand microbial swarms and films. The PI and his group will combine experiments on the bacteria Serratia marcescens and Escherichia coli, and the fungus Candida albicans, with multiphase continuum theories and stochastic agent-based simulations to understand the collective mechanics, particle transport and morphological adaptation in collectively moving swarms and rapidly growing fungal films. The specific aims are to: 1) interrogate and understand how micro-scale mechanics and transport, cell-cell interactions, and physicochemical interactions control the onset of collective multicellular swarms and films; 2) track evolution of mesoscale spatiotemporal properties and morphology in these composites and quantify any adaptations in response to external flow, chemical, and mechanical perturbations; 3) synthesize experiments with first-principles continuum theories, minimal models and stochastic simulations to identify physical mechanisms underlying the stability of bacteria/fungal microbiomes; 4) significantly enhance undergraduate and graduate bioengineering curricula by incorporating dry and wet laboratory components; 5) create a series of customizable modular graphics based standalone applications inspired by this research; and 6) provide research opportunities for underrepresented students.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.