Building a Proportional Cell: Statistical Physics of Subcellular Size Control

非技术性总结材料研究部，分子和细胞生物科学部和物理部为该奖项提供资金。该奖项支持细胞生物学基本问题的理论研究和教育，并对生物材料和统计物理学产生影响。所有活细胞的一个显著特征是它们包含许多亚细胞部分，称为细胞器，执行不同的功能。细胞器有不同的大小和形状，这些物理属性通常与它们的功能密切相关。例如，线粒体是充满脂质膜的隔室，脂质膜折叠在自身上许多次。大的膜支持蛋白质机器，这些机器嵌入膜中，其功能是制造细胞燃料分子。 类似地，细胞构建长度与细胞大小精确匹配的长聚合物电缆，并用于将材料从细胞的一侧运输到另一侧。这些观察激发了一个问题：细胞是如何组装这种三维结构的？虽然编码在细胞DNA中的基因携带着制造分子构建模块所需的信息，但它们如何自我组装成复杂的功能性三维结构仍然是未知的。 PI将使用亚细胞结构组装的数学模型来考虑这些基本问题。这些模型将根据几个合作生物实验室获得的实验数据进行测试。我们的目标将是确定共同的设计原则，导致一个明确的大小和形状的亚细胞结构的组装。细胞中的新实验将受到刺激，从而为制造自组装成特定形状和尺寸的合成材料提供潜在有用的见解。该研究的跨学科性质将为物理学生提供从事尖端生物研究的机会。它将为他们提供必要的技能，成为由生物学家和物理学家组成的跨学科研究团队的有效成员。这些技能对于未来的科学、技术、工程和数学劳动力尤为重要，因为社会面临的大多数重大问题都需要来自不同学科的科学家的共同努力。材料研究部、分子和细胞生物科学部以及物理部为该奖项提供资金。该奖项支持细胞生物学基本问题的理论研究和教育，并对生物材料和统计物理学产生影响。细胞中的亚细胞结构已经被观察了数百年，但直到最近，我们才开发出实验工具来解决有关它们的关键问题，例如：细胞器如何获得其特定形状？细胞如何控制其数量和大小？细胞如何“决定”它应该有多少线粒体？ 一个细胞是如何构建具有精确排列的部分的结构的，比如肌肉中的肌节，它的肌动蛋白细丝与肌球蛋白纤维交叉排列。 细胞骨架提供了一个特别富有成效的竞技场，在其中开发定量模型，解决这些问题的形态。也就是说，多年来，生物学家已经获得了大量关于细胞骨架结构和动力学的定量信息。这项工作已经产生了组成细胞骨架的分子的部分列表，以及这些分子如何相互作用，而这些相互作用如何在细胞内的空间和时间中协调的问题在很大程度上仍然没有答案。 PI将使用理论物理和数学来开发一种通用语言，用于描述细胞骨架结构的各种尺寸控制机制。亚细胞结构的组装将作为一个随机过程进行研究，该过程涉及不同的分子组分，并且将研究细胞用于控制其大小的数学上不同的反馈机制。拟议的研究将推进统计物理学，细胞生物学和生物材料领域。拟议的理论研究的关键特征之一是与实验室密切合作，研究酵母中肌动蛋白结构的组装动力学，小鼠毛细胞中纤毛的组装，以及蠕虫C. elegans发育中胚胎的核仁。它还将有助于培养对细胞生物学基本问题感兴趣的理论物理学家。

NONTECHNICAL SUMMARYThe Division of Materials Research, the Division of Molecular and Cellular Biosciences, and the Physics Division contribute funds to this award. This award supports theoretical research and education on fundamental questions of cell biology with implications for biomaterials and statistical physics. A remarkable feature of all living cells is that they contain many subcellular parts called organelles that perform different functions. Organelles come in different sizes and shapes and these physical attributes are often intimately related to their function. For example, mitochondria are compartments filled with lipid membranes folded upon themselves many times over. The large membrane supports protein machines that are imbedded in the membrane and whose function is to make cellular fuel molecules. Similarly, cells build long polymer cables of length precisely matched to the size of the cell, and are used to transport materials from one side of the cell to the other. These observations motivate the question: How do cells assemble such three-dimensional structures? While genes encoded in the cell's DNA carry the information needed to make the molecular building blocks, how they self-assemble into intricate and functional three-dimensional structures remains largely unknown. The PI will consider these fundamental questions using mathematical models for assembly of subcellular structures. These models will be tested against experimental data obtained by several collaborating biology labs. The goal will be to identify common design principles for assembly that lead to sub-cellular structures of a well-defined size and shape. New experiments in cells will be stimulated leading to potentially useful insights for making synthetic materials which self-assemble into specific shapes and sizes. The interdisciplinary nature of the research will provide opportunities for physics students to engage in cutting edge biological research. It will provide them with skills necessary to be effective members of an interdisciplinary research team consisting of biologists and physicists. These skills are particularly important for the science, technology, engineering and mathematics workforce of the future since most of the big problems facing society will require a concerted effort of scientists from different disciplines. TECHNICAL SUMMARYThe Division of Materials Research, the Division of Molecular and Cellular Biosciences, and the Physics Division contribute funds to this award. This award supports theoretical research and education on fundamental questions of cell biology with implications for biomaterials and statistical physics. Subcellular structures in cells have been observed for hundreds of years and yet it is only recently that we have developed the experimental tools to address key questions about them, such as: How do cellular organelles obtain their specific shapes? How do cells control their number and size? How does a cell 'decide' how many mitochondria should it have? How does a cell construct structures with precisely arranged parts, such as sarcomeres in muscle with its regimented arrays of actin filaments interdigitated with myosin fibers? The cytoskeleton provides a particularly fruitful arena in which to develop quantitative models that address these questions of morphology. Namely, over many years biologists have obtained a wealth of quantitative information about the structure and dynamics of the cytoskeleton. This work has produced a parts list of molecules that the cytoskeleton is made of, and how these molecules interact, while the question of how these interactions are coordinated in space and time inside the cell remains largely unanswered. The PI will use theoretical physics and mathematics to develop a common language for describing the various size control mechanisms of cytoskeleton structures. An assembly of sub-cellular structures will be investigated as a stochastic process that involves different molecular components and mathematically different feedback mechanisms that cells employ to control their size will be studied. The proposed research will advance the fields of statistical physics, cell biology, and biomaterials. One of the key features of the proposed theoretical research is a close collaboration with experimental labs that study assembly dynamics of actin structures in yeast, the assembly of cilia in mouse hair cells, and of nucleoli in developing embryos of the worm C.elegans. It will also help train theoretical physicists interested in working on fundamental problems in cell biology.