RUI: Connecting Microtubule Mechanical and Structural Properties using a Novel Millimeter-length Gliding Assay

大多数动物和植物细胞含有一个小的，管状结构的网络，恰当地命名为微管，参与各种细胞功能，包括细胞成分的组织，细胞内的运输和细胞分裂。 虽然大多数细胞中的微管具有相同的直径（约25 nm），但一些特殊的细胞类型含有不同直径的微管。 在C.例如，秀丽线虫调节微管直径，使其比同一生物体中其他细胞的微管直径大40%。微管的一个功能特性是它们的硬度或刚性。 物理理论预测，大直径的微管应该比小直径的微管更坚硬。这项研究旨在了解不同直径的微管的机械特性（刚度或刚度）是否足够重要，以在不同的生物功能中发挥作用。 特别是，这项工作将以非常高的精度测量单个微管的刚度和直径，以确定不同直径的微管之间的机械差异是否超过相同直径的微管的机械变化。 如果是这样的话，大直径微管的刚性增加是生物学功能的候选者;如果不是，微管刚性的异质性表明微管直径的调节是出于非机械目的。 该研究涉及开发新的光学显微镜工具，能够在这些分子移动毫米距离时以纳米精度跟踪单个分子。 虽然这些工具将被开发来解决微管刚性的问题，但它们的应用超出了这项工作，可能包括长距离细胞运动和细胞内运输。更广泛的影响该项目将提供研究经验，科学著作权，并为本科生在三年内，无论是在夏季和学年的演讲机会。来自物理科学和生命科学的学生将共同努力，着眼于在本科阶段开发跨学科研究的可传播模型。由于劳伦斯大学的少数民族入学人数不断增加（自2000年以来增加了153%）和PI指导女学生的记录，这项研究将积极影响博士学位管道中代表性不足的群体的参与。开发的实验装置也将用于招募有前途的高中学生到LU物理和生物化学课程。

Intellectual MeritMost animal and plant cells contain a network of small, tube-like structures, aptly named microtubules, that are involved in a variety of cell functions, including organization of cell components, transport within cells, and cell division. While microtubules in most cells have the same diameter (approximately 25 nm), some specialized cell types contain microtubules with different diameters. Cells implicated in mechanosensation in C. elegans, for example, regulate microtubule diameters to be 40% larger than microtubules in other cells in the same organism. One functional property of microtubules is their stiffness or rigidity. Physical theory predicts that large diameter microtubules should be substantially more rigid than small diameter microtubules. This research seeks to understand whether the mechanical properties (stiffness or rigidity) of microtubules with different diameters are significant enough to play a role in different biological functions. In particular, this work will measure the rigidity and diameter of single microtubules with very high precision to determine whether mechanical differences between microtubules with different diameters outweigh mechanical variations of microtubules with the same diameter. If so, the increased rigidity of large diameter microtubules is a candidate for biological function; if not, the heterogeneity of microtubule rigidities suggests that microtubule diameter is regulated for a non-mechanical purpose. The research involves development of new light microscopy tools capable of following single molecules with nanometer precision as these molecules move through millimeter distances. While these tools will be developed to address the question of microtubule rigidity, they have applications beyond this work, potentially including long-distance cell motility and intracellular transport. Broader ImpactThe project will provide research experiences, scientific authorship, and presentation opportunities for undergraduates over three years, both during the summer and academic year. Students from the physical sciences and life sciences will work together, with an eye to developing a disseminatable model of interdisciplinary research at the undergraduate level. Because of Lawrence University's increasing minority enrollment (153% increase since 2000) and PI's record of mentoring women students, this research will positively impact the engagement of underrepresented groups in the PhD pipeline. The experimental apparatus developed will also be used to recruit promising high school students to the LU Physics and Biochemistry programs.