Spindle Flux and Mechanics

细胞是生命的基本单位，所有的细胞都是通过细胞分裂而产生的。为了确保每个子细胞收到一整套生命指令，细胞首先复制它们的遗传物质(DNA)，然后将一个副本移动到每个子细胞。细胞每天执行这项任务数百万次。用于细胞分裂的机器被称为有丝分裂纺锤体。有丝分裂纺锤体是组织和排列染色体DNA并将其分离到子细胞中所必需的。这个过程对所有生物的形成、发育和维持都是极其重要的。有丝分裂纺锤体的自组织不能仅用生物学来理解。相反，它需要了解支配有丝分裂纺锤体组装和功能的潜在物理原理。这里进行的研究将应用液晶(与电脑和手机屏幕上发现的相同的液晶)自组织背后的物理概念来了解有丝分裂纺锤体在没有外部指令的情况下自我组织的能力。了解构成细胞组织的基本生命规则将导致对细胞如何工作的新知识，以及帮助我们理解并最终与疾病作斗争的新见解。该项目将涉及到附近社区的8年级和9年级女孩，以及对本科生和研究生的跨学科培训。这项建议的科学目标是了解微管周转和交联物如何控制有丝分裂纺锤体的组织和动力学。有丝分裂纺锤体是一种高密度的交联微管组织，它应该足以阻止微管固有的动态不稳定性以及结构内细丝的移动性。然而，已有研究表明，纺锤体经历了从染色体到两极的整体流动。人们注意到，这种流动在染色体上比在两极更快。研究人员提出的一个新模型提出，磁通是使染色体附近的纺锤体流态化的必要过程，在染色体附近，需要增强运动来纠正错误。由于助熔剂过程中交联剂的含量较高，导致粘附性增加，磁极上的助焊剂减少。这个令人兴奋的新模型创造了一个新的物理框架，开始探索使有丝分裂纺锤体动态自组织的基本原理。这项拟议的工作将使用定量光学显微镜和遗传操作来直接测试假设的模型。这些测试将揭示关于主轴内部工作的新信息。该提议直接回应了现代生物学研究的几个重要方面，包括跨尺度整合，从单分子到复杂结构和整个细胞。活性物质实验直接涉及使用最少的纯化成分合成类生命系统。从物理学的角度来看，类生命系统的合成对于理解生物的非平衡过程是必不可少的，这些过程耦合到自组织、感知和对刺激的反应。这是物理学和材料研究的前沿领域，将揭示基础细胞生物学的新知识。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Cells are the fundamental unit of life and all cells arise by cell division. To ensure that each daughter cell receives a complete set of the instructions for life, cells first duplicate their genetic material (DNA) and then move one copy to each daughter cell. Cells perform this task millions of times each day. The machine utilized for cell division is called the mitotic spindle. The mitotic spindle is required to organize and arrange the chromosomal DNA and segregate it into the daughter cells. This process is extremely important for the formation, development and maintenance of all living organisms. The self-organization of the mitotic spindle cannot be understood using biology alone. Rather, it requires the understanding of the underlying physical principles that govern the assembly and function of the mitotic spindle. The research conducted here will apply physical concepts behind self-organization of liquid crystals (the same liquid crystals found in computer and cell phone screens) to understand the ability of the mitotic spindle to organize itself in the absence of outside instructions. Understanding the fundamental rules of life that underlie cellular organization will result in new knowledge about how cells work as well as new insights to help us understand and ultimately fight diseases. The project will involve outreach to 8th and 9th grade girls in the nearby community, along with interdisciplinary training of undergraduates and graduate students.The scientific objective of this proposal is to understand how microtubule turnover and crosslinking control the organization and dynamics of the mitotic spindle. The mitotic spindle is a high-density organization of cross-linked microtubules which should be enough to stall the inherent microtubule dynamic instability as well as the mobility of the filaments within the structure. Yet, it has been shown that the spindle undergoes overall flux from the chromosomes toward the poles. This flux has been noted to be faster at the chromosomes than at the poles. A new model put forth by the investigators proposes that the flux is an essential process to fluidize the spindle near chromosomes where enhanced motion is needed to error correction. Flux decreases at the poles because of increased adhesion due to higher levels of crosslinkers put there by the process of flux. This exciting new model creates a new physical framework to begin exploring the underlying fundamental principles that enable the dynamic self-organization of the mitotic spindle. The proposed work will directly test the hypothesized model using quantitative light microscopy and genetic manipulations. These tests will reveal new information on the inner workings of the spindle. The proposal directly responds to several important aspects of modern biological research including integrating across scales, from single molecules to complex structures and whole cells. The active matter experiments directly address the synthesis of life-like systems using minimal purified components. From a physics perspective, the synthesis of life-like systems are essential to understanding the non-equilibrium processes of biology that couple to self-organize, sense, and respond to stimuli. This is a frontier area of physics and materials research, which will uncover new knowledge about fundamental cell biology.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.