Collaborative Research: Are Muscle Fibers Just the Right Size?

许多类型的肌肉都是通过增加细胞大小来生长的，例如幼年动物的细胞很小，但在发育过程中它们可能会变得相当大。这导致氧气和营养物质从血液到细胞的运输以及细胞内代谢物在细胞内扩散的限制发生变化。因此，在发育过程中，肌纤维必须保持功能，同时导航多维能量景观，包括分子运输，ATP需求，行为，体重范围和进化历史。这项工作将解决这样一个问题：肌肉细胞是否在不影响功能的情况下达到最大？P.I.s将研究多种鱼类和甲壳类动物生长过程中肌肉结构和功能的变化。实验目的是：(1)使用光学和电子显微镜来表征细胞结构；(2)将磁共振波谱应用于体内和离体肌肉制剂，以确定ATP的转换速率；(3)构建一个反应-扩散数学模型，将氧通量和细胞内代谢物扩散通量整合在一起；(4)使用该模型来定义纤维大小和ATP转换的任何组合的代谢功能极限。预计随着动物的生长，肌肉细胞会接近分子运输限制，但所有发育阶段都会受到限制的影响，最终只会在成年动物中遇到这种限制。这是一个具有广泛影响的合作研究项目。主要重点将放在培养本科生和研究生，包括代表性不足的群体。这种训练将是隐性跨学科的，将涉及工程和生物学生。这些学生将参与实验方法，包括使用国家高磁场实验室最先进的磁共振仪器，以及严格的数学建模和计算机编程。

Many types of muscle grow by increasing cell size, such that in juvenile animals the cells are small, but during development they may become quite large. This leads to changing constraints both on the transport of oxygen and nutrients from the blood to the cell and intracellular metabolite diffusion across the cell. Thus, during development muscle fibers must preserve function while navigating a multi-dimensional energetic landscape that encompasses molecular transport, ATP demand, behavior, body mass range and evolutionary history. This work will address the question: Are muscle cells as big as they can be without compromising function? The P.I.s will examine changes in muscle structure and function during growth in a diversity of fishes and crustaceans. The experimental objectives are: (1) to use light and electron microscopy to characterize cell architecture, (2) to apply magnetic resonance spectroscopy to in vivo and ex vivo muscle preparations to determine rates of ATP turnover, (3) to construct a reaction-diffusion mathematical model that integrates oxygen flux and intracellular metabolite diffusive flux, and (4) to use the model to define the limits of metabolic function for any combination of fiber size and ATP turnover. It is expected that muscle cells approach molecular transport limitation as the animals grow, but that all stages of development will be influenced by limits that are ultimately encountered only in the adults. This is a collaborative research project with a variety of broader impacts. A primary emphasis will be on the training of undergraduate and graduate students, including underrepresented groups. This training will be implicitly cross-disciplinary, and will involve both engineering and biology students. These students will be involved in experimental approaches that include the use of state-of-the-art magnetic resonance instruments at the National High Magnetic Field Laboratory, as well as rigorous mathematical modeling and computer programming.