CAREER: Nonequilibrium organization in epithelial sheets

职业：上皮片中的非平衡组织

• 批准号: 1056456
• 负责人: David K Lubensky
• 金额: $ 53.5万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1056456&HistoricalAwards=false
• 关键词: CAREER; Nonequilibrium; organization; epithelial; sheets

TECHNICAL SUMMARYThe Division of Materials Research and the Division of Molecular and Cellular Biosciences contribute funds to this CAREER award. This award supports theoretical research and education that applies ideas from condensed matter physics to understand the organization of active cellular systems, with epithelial sheets in biology serving as a particular inspiration. These quasi-two-dimensional, planar assemblies of mechanically coupled cells are the basic building blocks of most tissues and organs, and their movements and rearrangements are at the root of much of animal morphogenesis. Topics to be studied include the mechanisms that array cells in the sheets in intricate, reproducible patterns and the ways that cells interact to induce large-scale tissue movements.Recent years have seen growing interest in the statistical physics of systems far from thermodynamic equilibrium, also called active systems, including in particular biologically-inspired systems like collections of molecular motors and cytoskeletal filaments. These efforts have lead to a number of theoretical advances, but so far, most work has focused either on systems in an infinite continuous space or on simple geometries meant to mimic the interiors of individual cells. Higher animals and humans, however, are made up of complex tissues consisting of many cells whose mechanical interactions play a central role in regulating myriad biological processes. Despite the fact that each of these cells is a living, active system, models at the tissue scale have with a few exceptions been limited to descriptions based on the equilibrium mechanics of passive solids. With this award, the PI will seek to bridge this gap. Specifically, he will: 1. Study generic instabilities of cells in epithelial sheets, including those tied to cell polarization, which has strong analogies with magnetic ordering in equilibrium systems. 2. Formulate phenomenological models of interacting active cells dictated by symmetries and conservation laws. 3. Construct 'mesoscopic' models of active gels within mechanically coupled cells. These models will open the way to studying recently discovered subcellular organization in epithelia such as traveling waves of actin density that propagate from cell to cell. This research program will lay the groundwork for more detailed studies of specific biological epithelia, including those implicated in human developmental defects, and may provide the inspiration for the construction of active biomimetic systems that can replicate the extraordinary order, control, and accuracy that characterizes their biological inspirations.This award will support the interdisciplinary education of undergraduate and graduate students; the PI will make a concerted effort to recruit members of under-represented minorities to his research group. The award will also support the development of a museum exhibit and a series of public lectures on topics related to the research and the refinement of course materials to support the introduction of peer instruction methods in upper-level physics courses.NON-TECHNICAL SUMMARYThe Division of Materials Research and the Division of Molecular and Cellular Biosciences contribute funds to this CAREER award. This award supports theoretical research and education that applies ideas from condensed matter physics to understand the organization of active cellular systems. Physicists have developed a number of powerful theoretical techniques to understand the origins of regular, periodic order in inert, physical systems such as solids or liquids. Similar-seeming order is seen in biological systems, but it is unclear to what extent the same mechanisms drive the organization of living cells which constantly consume energy. The research funded by this award will seek to answer this question for a particular class of biological systems, epithelial sheets. These planar assemblies of mechanically coupled cells are the basic building blocks of most tissues and organs, and their movements and rearrangements are central to the development of adult animals from fertilized eggs. Specifically, the PI will: 1) Classify the instabilities by which groups of cells in epithelial can suddenly rearrange their packing. 2) Understand what physical properties of epithelia are independent of their detailed microscopic organization. 3) Develop theoretical techniques that will connect biochemical and biophysical knowledge about particular cellular components to large-scale organization. This research program will lay the groundwork for more detailed theoretical studies of specific biological epithelia, including those implicated in human developmental defects, and may provide theoretical guidance for the construction of active biomimetic systems that can replicate the extraordinary order, control, and accuracy that characterizes their biological inspirations.This award supports the interdisciplinary education of undergraduate and graduate students; the PI will make a concerted effort to recruit members of under-represented minorities to his research group. It also supports the development of a museum exhibit and a series of public lectures on topics related to the research and the refinement of course materials to support the introduction of peer instruction methods in upper-level physics courses.

技术总结材料研究部和分子和细胞生物科学部为该职业奖提供资金。该奖项支持理论研究和教育，应用凝聚态物理学的思想来理解活性细胞系统的组织，生物学中的上皮细胞作为一个特别的灵感来源。 这些准二维的、平面的机械耦合细胞集合体是大多数组织和器官的基本构建块，它们的运动和重排是许多动物形态发生的根源。 研究课题包括细胞排列成复杂的、可重复的模式的机制，以及细胞相互作用诱导大规模组织运动的方式。近年来，人们对远离热力学平衡的系统（也称为主动系统）的统计物理学越来越感兴趣，特别是生物启发的系统，如分子马达和细胞骨架细丝的集合。 这些努力导致了许多理论上的进步，但到目前为止，大多数工作都集中在无限连续空间中的系统或简单的几何形状上，旨在模仿单个细胞的内部。 然而，高等动物和人类是由许多细胞组成的复杂组织组成的，这些细胞的机械相互作用在调节无数生物过程中发挥着核心作用。 尽管这些细胞中的每一个都是一个活的、主动的系统，但组织尺度的模型除了少数例外，都局限于基于被动固体的平衡力学的描述。 有了这个奖项，PI将寻求弥合这一差距。 具体来说，他将：1。 研究上皮层中细胞的一般不稳定性，包括与细胞极化有关的不稳定性，这与平衡系统中的磁有序有很强的相似性。 2. 制定由对称性和守恒定律决定的相互作用的活性细胞的现象学模型。 3. 在机械耦合的细胞内构建活性凝胶的“介观”模型。 这些模型将为研究最近发现的上皮细胞中的亚细胞组织开辟道路，例如从细胞传播到细胞的肌动蛋白密度的行波。 该研究计划将为更详细地研究特定的生物上皮细胞奠定基础，包括那些与人类发育缺陷有关的上皮细胞，并可能为构建主动仿生系统提供灵感，这些系统可以复制其生物灵感所特有的非凡秩序，控制和准确性。该奖项将支持本科生和研究生的跨学科教育; PI将共同努力招募代表性不足的少数民族成员加入其研究小组。 该奖项还将支持博物馆展览的发展和一系列与研究相关的主题的公开讲座，以及课程材料的改进，以支持在高级物理课程中引入同伴指导方法。非技术总结材料研究部和分子和细胞生物科学部为该职业奖提供资金。该奖项支持理论研究和教育，应用凝聚态物理学的思想来理解活跃的细胞系统的组织。 物理学家已经开发出许多强大的理论技术来理解惰性物理系统（如固体或液体）中规则的周期性秩序的起源。 在生物系统中也可以看到类似的秩序，但目前还不清楚在何种程度上相同的机制驱动着不断消耗能量的活细胞的组织。 该奖项资助的研究将寻求为一类特定的生物系统（上皮层）回答这个问题。 这些机械耦合细胞的平面组件是大多数组织和器官的基本组成部分，它们的运动和重排是从受精卵发育成成年动物的核心。 具体而言，PI将：1）通过上皮细胞中的细胞组可以突然重新排列它们的包装来对不稳定性进行分类。 2)了解上皮细胞的哪些物理特性与其详细的微观组织无关。 3)发展理论技术，将有关特定细胞成分的生物化学和生物物理知识与大规模组织联系起来。 该研究计划将为特定生物上皮细胞的更详细的理论研究奠定基础，包括那些与人类发育缺陷有关的上皮细胞，并可能为构建主动仿生系统提供理论指导，这些系统可以复制其生物灵感所特有的非凡秩序，控制和准确性。该奖项支持本科生和研究生的跨学科教育; PI将共同努力招募代表性不足的少数民族成员加入其研究小组。 它还支持开发一个博物馆展览和一系列与研究和完善课程材料有关的主题的公开讲座，以支持在高级物理课程中引入同伴指导方法。