Intracellular Force Generation Measured Through Nuclear Particle Tracking

通过核粒子跟踪测量细胞内力的产生

基本信息

批准号：
1634888
负责人：
Kris Dahl
金额：
$ 38.74万
依托单位：
Carnegie-Mellon University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2016
资助国家：
美国
起止时间：
2016-11-01 至 2020-10-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1634888&HistoricalAwards=false
关键词：
Intracellular Force Generation Measured Through

项目摘要

Individual molecular motors generate very small forces within cells, but the coordination and integration of these forces is responsible for large scale movements of an organism. The study of forces that a cell can generate has been of wide interest for decades but has been limited to visualizing how the environment around the cell deforms in response to the cell pulling. However, with proper image analysis tools for removing intrinsic movements of the cell itself, fluctuations within the cell nucleus also provide a metric for quantifying forces generated inside the cell. This methodology is in its infancy and will require effort to fully characterize and compare to established techniques. By determining the forces that cells generate, including if neighboring cells generate different forces, it is possible to understand how microscopic units of the body work together to form larger dynamic structures. Specifically, this is important in tissue formation during early embryonic development and in multicellular dysfunction associated with different disease states including cancer and vascular disease. The project will integrate undergraduate professional development with K-3 science outreach programs. The PI will develop a program to teach ethics to undergraduate students focusing on Comparative Ethics for Biomedical Engineers contrasting the different priorities of the patient, science and society.By removing intrinsic cellular translocation and rotation using image analysis post-processing, it is possible to correlate movements within the nucleus with force generation of the actin-myosin cytoskeleton. Utilizing this newly developed technique of intranuclear particle tracking it may be possible to measure how cells propagate mechanical stimuli applied within a monolayer through cell structures on short timescales before diffusion can occur and on long timescales as interconnected cells begin to adapt cellular structures in response to stress. This intracellular force transduction measurement within multicellular systems will allow investigation of heterogeneous tissue systems where traction force microscopy and other contemporary measurements have experimental limitations. Specifically, this investigation will include examining force transduction through a sheet of endothelial cells growing on smooth muscle cells in different vascular states in and inside cells of C. elegans during embryo development.

单个分子电动机在细胞内产生非常小的力，但是这些力的协调和整合是造成生物体的大规模运动。几十年来，对细胞可以产生的力的研究一直引起人们的关注，但仅限于可视化细胞周围的环境对细胞拉的响应如何变形。但是，使用适当的图像分析工具来消除细胞本身的内在运动，细胞核内的波动也提供了一个度量，用于量化细胞内部产生的力。这种方法还处于起步阶段，需要努力与已建立的技术进行充分表征和比较。通过确定细胞产生的力，包括如果相邻细胞产生不同的力，就可以了解体的显微镜单位如何共同形成更大的动态结构。具体而言，这在早期胚胎发育期间的组织形成以及与不同疾病状态有关的多细胞功能障碍（包括癌症和血管疾病）中很重要。该项目将将本科专业发展与K-3科学外展计划相结合。 PI将制定一项计划，以教导专注于生物医学工程师的比较伦理学的本科生，以对比患者，科学和社会的不同优先事项。通过使用图像分析后处理后处理，可以消除固有的细胞易位和旋转，可以将核中的运动与肌肉的生成与actt cytossposemossposemose的生成相关联。利用这种新开发的核内粒子跟踪技术，可能可以测量细胞如何通过在扩散前的短时尺度上通过细胞结构在单层中传播机械刺激，并且在长时间尺度上可能会在较长的时间表上随着互连细胞开始适应压力的细胞结构，以响应压力。多细胞系统内的这种细胞内力转导测量将允许研究牵引力显微镜和其他当代测量的异质组织系统具有实验性局限性。具体而言，这项研究将包括通过在胚胎发育过程中在秀丽隐杆线虫内外不同血管状态的平滑肌细胞上生长在平滑肌细胞上的一组内皮细胞的力转移。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Determining mechanical features of modulated epithelial monolayers using subnuclear particle tracking

使用亚核粒子追踪确定调制上皮单层的机械特征

DOI：
10.1242/jcs.216010
发表时间：
2018
期刊：
Journal of Cell Science
影响因子：
4
作者：
Armiger, Travis J.;Lampi, Marsha C.;Reinhart-King, Cynthia A.;Dahl, Kris Noel
通讯作者：
Dahl, Kris Noel

Concentric organization of A- and B-type lamins predicts their distinct roles in the spatial organization and stability of the nuclear lamina

DOI：
10.1073/pnas.1810070116
发表时间：
2019-03-05
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Nmezi, Bruce;Xu, Jianquan;Padiath, Quasar S.
通讯作者：
Padiath, Quasar S.

Piperazine Derivatives Enhance Epithelial Cell Monolayer Permeability by Increased Cell Force Generation and Loss of Cadherin Structures

哌嗪衍生物通过增加细胞力的产生和钙粘蛋白结构的损失来增强上皮细胞单层通透性

DOI：
10.1021/acsbiomaterials.9b01660
发表时间：
2019
期刊：
ACS Biomaterials Science & Engineering
影响因子：
5.8
作者：
Zheng, Shiyuan;Lavrenyuk, Kirill;Lamson, Nicholas G.;Fein, Katherine C.;Whitehead, Kathryn A.;Dahl, Kris Noel
通讯作者：
Dahl, Kris Noel

Cells with Higher Cortical Membrane Tension Are More Sensitive to Lysis by Biosurfactant Di-rhamnolipids

皮质膜张力较高的细胞对生物表面活性剂二鼠李糖脂的裂解更敏感