ERI: Multi-Scale Modeling of Cell-Matrix Mechanical Interactions in Endothelial Cell Network Assembly

ERI：内皮细胞网络组装中细胞-基质机械相互作用的多尺度建模

• 批准号: 2138672
• 负责人: Kinjal Dasbiswas
• 金额: $ 20万
• 依托单位: University of California - Merced
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2138672&HistoricalAwards=false
• 关键词: ERI; Multi; Scale; Modeling; Cell

This Engineering Research Initiation (ERI) award will support research about how mammalian cells organize into functional multicellular structures. Specifically, how cells organize through physical cues will be revealed. The focus will be on self-organized cell networks. These networks are known to occur prior to blood vessel formation. They require specific properties to successfully transport nutrients and oxygen. Tissue can be engineered in synthetic environments if the conditions are right. Those conditions include a combination of cells, materials, and chemical factors. Engineering these tissues by mechanical manipulations of the cell network can also have effects. Better understanding these mechanisms means that damaged tissues can ultimately be restored and replaced. The results of this research will contribute to both scientific understanding and national health. The multidisciplinary research approach will be combined with educational activities. These activities will introduce students to quantitative approaches in the life sciences. This project will also contribute to the recruitment, retention, and training of students in science and engineering fields in the underserved Central Valley region of California. The research will use mathematical modeling and agent-based computation to identify the multicellular structures that result from intercellular interactions mediated by the elastic deformations of the extracellular substrate. A cell can exert contractile traction forces to deform or restructure its material environment. The modeling will combine individual cell motility with cell-cell mechanical interactions through their mutual deformations of the substrate. The substrate will be modeled at multiple scales as a linear elastic continuum as well as a discrete, fibrous medium. The model cell networks obtained in simulation will be analyzed quantitatively to obtain crucial metrics related to transport functions such as the number of junctions, branches and loops, and their space coverage. These quantitative measures will predict how the cell network structure and function depend on substrate mechanical properties. These results will be compared with analysis of available experimental data on vascular cell networks on soft substrates. The modeling developed during this project can be extended in the future to describe the self-assembly of other cell types in other culture geometries including three-dimensional assemblies.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.

该工程研究启动（ERI）奖将支持有关哺乳动物细胞如何组织成功能性多细胞结构的研究。具体来说，细胞如何通过物理线索组织将被揭示。重点将放在自组织细胞网络上。已知这些网络在血管形成之前发生。它们需要特定的特性来成功地运输营养物质和氧气。如果条件合适，组织可以在合成环境中进行工程改造。这些条件包括细胞、材料和化学因素的组合。通过细胞网络的机械操作来工程化这些组织也可以产生效果。更好地理解这些机制意味着受损组织最终可以恢复和替换。这项研究的结果将有助于科学认识和国民健康。多学科研究方法将与教育活动相结合。这些活动将向学生介绍生命科学中的定量方法。该项目还将有助于招聘，保留，并在加州服务不足的中央谷地区的科学和工程领域的学生培训。该研究将使用数学建模和基于代理的计算来识别由细胞外基质的弹性变形介导的细胞间相互作用产生的多细胞结构。细胞可以施加收缩牵引力来变形或重构其物质环境。该建模将通过基底的相互变形将单个细胞运动性与细胞-细胞机械相互作用结合联合收割机。该基板将在多个尺度上建模为线性弹性连续体以及离散的纤维介质。将对模拟中获得的模型细胞网络进行定量分析，以获得与传输功能相关的关键指标，例如连接点，分支和环路的数量及其空间覆盖范围。这些定量测量将预测细胞网络结构和功能如何取决于基板的机械性能。这些结果将进行比较与分析现有的实验数据血管细胞网络上的软基板。在这个项目中开发的模型可以在未来扩展到描述其他细胞类型在其他培养几何形状中的自组装，包括三维组装。这个奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。