Role of vimentin in mammalian cell motility

波形蛋白在哺乳动物细胞运动中的作用

• 批准号: 10582235
• 负责人: Alison Elise Patteson
• 金额: $ 19.67万
• 依托单位: SYRACUSE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-16 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582235
• 关键词: 3-Dimensional; Actins; Address; Adhesions; Cell Communication; Cell Nucleus; Cell surface; Cells; Cytoskeleton; Disease; Embryonic Development; Environment; Equipment; Extracellular Matrix; F-Actin; Focal Adhesions; Funding; Goals; Health; Human; Integrins; Intermediate Filament Proteins; Intermediate Filaments; Maintenance; Malignant Neoplasms; Mammalian Cell; Mechanics; Mediating; Microfabrication; Microfluidics; Microtubules; Nanotechnology; Neoplasm Metastasis; Nuclear; Physiological; Play; Polymers; Positioning Attribute; Process; Role; Stress Fibers; Surface; System; Techniques; Technology; Testing; Time; Tissues; Travel; Vimentin; cell motility; cost; design; instrument; migration; novel; resilience; wound healing

ABSTRACT Cell migration is essential to many fundamental processes, including embryonic development, wound repair, and cancer metastasis. Central to this process is the cellular cytoskeleton comprised of three polymeric networks: F-actin, microtubules, and intermediate filaments (IFs). Vimentin is an IF protein that is essential to the mechanical resilience of cells and regulates cross-talk amongst the cytoskeleton, but its role in how cells squeeze through small pores in tissues is poorly understood. We have shown that loss of vimentin enhances cell motility through three-dimensional 3D micro-fluidic channels and protects the nucleus from damage during migration. Vimentin is thought to play a distinct role in the transfer of forces from cell surface matrix adhesions to the nuclear surface, but new evidence suggests that vimentin may also play a more active role in persistent cell motility via its interactions with actin stress fiber formation and microtubule positioning. Still, the specific mechanisms by which vimentin enables 3D migration through dense tissue remains unclear. This project addresses the overarching question: how does vimentin influence cytoskeletal functions, adhesions with the extracellular matrix, and cell-cell interactions to coordinate 3D cell migration? To address this question, we are pursuing three sub-projects. First, we are determining the effects of vimentin in cytoskeletal- mediated 3D cell motility. Second, we are identifying vimentin’s role in integrin expression and focal adhesion activation, and third, we are identifying the mechanisms by which vimentin mediates collective cell migration through extracellular matrix networks. To achieve our project goals, we request supplemental funding to acquire a PRIMO photopatterning system to support our studies of vimentin’s role in cell migration through 3D tissue-like environments. We are currently traveling one-way 1-hr from Syracuse to Cornell Nanotechnology Facility in Ithaca NY to use microfabrication equipment, placing undue cost and time barriers for this project. For this project to be successful, we need more access to microfabrication technology to rapidly test and develop designs for cell migration studies, which the PRIMO instrument will provide. We expected that these projects will determine new functional roles of vimentin in cell migration, which has important implications for understanding healthy tissue maintenance and diseases that progress by the migration of cells through tissues.

摘要 细胞迁移对许多基本过程至关重要，包括胚胎发育，伤口修复， 和癌症转移。这个过程的中心是由三个聚合物组成的细胞骨架 网络：F-肌动蛋白，微管和中间丝（IF）。波形蛋白是一种IF蛋白， 细胞的机械弹性，并调节细胞骨架之间的串扰，但它在细胞如何 通过组织中的小孔进行挤压的方法知之甚少。我们已经证明，波形蛋白的丢失增强了 细胞运动通过三维3D微流体通道，并保护细胞核免受损伤， 迁移波形蛋白被认为在细胞表面基质粘附力的传递中起着独特的作用 但新的证据表明，波形蛋白也可能在持续的细胞核表面发挥更积极的作用。 细胞运动通过其与肌动蛋白应力纤维形成和微管定位的相互作用。但是，具体 波形蛋白使3D迁移通过致密组织的机制仍不清楚。这个项目 解决了首要问题：波形蛋白如何影响细胞骨架功能，粘附与 细胞外基质和细胞间相互作用来协调3D细胞迁移？为了解决这个 问题，我们正在进行三个次级项目。首先，我们确定波形蛋白在细胞骨架中的作用- 介导的3D细胞运动。其次，我们正在确定波形蛋白在整合素表达和粘着斑中的作用。 第三，我们正在确定波形蛋白介导集体细胞迁移的机制 通过细胞外基质网络。为了实现我们的项目目标，我们要求补充资金， 获得一个PRIMO标记系统，以支持我们对波形蛋白在细胞迁移中作用的研究 through通过3D tissue-like组织environments环境.我们目前正在从锡拉丘兹到康奈尔的单程1小时旅行 位于纽约伊萨卡的纳米技术设施将使用微细加工设备，这将带来不必要的成本和时间障碍 为这个项目。为了这个项目的成功，我们需要更多的微制造技术， 测试和开发细胞迁移研究的设计，PRIMO仪器将提供。我们预计 这些项目将确定波形蛋白在细胞迁移中的新功能作用，这具有重要意义。 了解健康组织的维护和疾病的进展，通过迁移的细胞， 组织中