Understanding Why Cells Choose to Migrate Towards the Cathode: Directing Cell Motility Using Electric Fields

了解细胞为何选择向阴极迁移：利用电场引导细胞运动

• 批准号: 2001226
• 负责人: Zachary Gagnon
• 金额: $ 11.07万
• 依托单位: Texas A&M Engineering Experiment Station
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2001226&HistoricalAwards=false
• 关键词: Understanding; Why; Cells; Choose; Migrate

PI: Gagnon, Zachary RProposal #: 1605553How a cell senses, responds, and moves towards or away from an external cue is central to many biological and medical phenomena including embryogenesis, morphogenesis, immune response, wound healing and cancer metastasis. Electrotaxis, the phenomenon by which cells bias their motion directionally in response to an externally applied electrical field, is important in a number of cellular processes; however, the underlying physical mechanism of how electric fields influence cytoskeletal organization within the cell is unknown. The overall goal of the planned research is to determine the physical mechanisms responsible for initiating electrotaxis in cells. The goal will be achieved by observing electrotactic migration and quantifying the ion activity surrounding electrotaxing cells using precise microfluidic cell confinement chambers. Intellectual merit is based on the innovative strategy and fundamental significance in determining the physical entry point where electric fields are converted into a downstream chemical signal during cellular electrotaxis. Unlike traditional electrotaxis work that focuses on downstream signaling proteins, this project focuses on understanding the immediate influences of the electric field at the cell membrane. Educational impact is achieved through providing new courses and laboratory training for undergraduate and graduate students, outreach to high school students through the institutions "Engineering Innovation" program, engaging 6th - 8th grade students through the "Science Academy Technology" program in Baltimore and Charles City Middle Schools and broadening the participation of underrepresented groups in the proposed research projects through hands-on research and community outreach.How a cell senses, responds, and moves towards or away from an external cue is central to many biological and medical phenomena including embryogenesis, morphogenesis, immune response, wound healing and cancer metastasis. Many eukaryotic cells have internal compasses that allow them to sense these cues, often in the form of gradients of chemoattractant, voltage, or mechanical stress, and bias their motion in a specific direction. Electrotaxis, the phenomenon by which cells bias their motion directionally in response to an externally applied electrical field, is important in a number of cellular processes; however, the underlying physical mechanism of how electric fields are transduced into the cell to influence cytoskeletal organization is unknown. The overall goal of this proposal is to determine the relevant physical mechanisms responsible for initiating electrotaxis in cells. The goal will be achieved by observing electrotactic migration and quantifying the ion activity surrounding electrotaxing cells using precise microfluidic cell confinement chambers. The specific objectives are: 1) to develop and build microfluidic confinement geometries for cell membrane level analysis of electrokinetic ion flux during electrotaxis, 2) to quantify the electric field-induced membrane processes including ion-flow and ion channel activity during electrotaxis, and 3) to understand how downstream cell signaling is activated and transduced by these upstream electric field-induced events. The intellectual merit of the planned research is based on the innovative strategy and fundamental significance in determining the physical entry point where electric fields are transduced into a downstream chemical signal during cellular electrotaxis. Unlike traditional electrotaxis work that focuses on downstream signaling proteins, this project focuses on understanding the immediate influences of the electric field at the cell membrane. Educational impact is achieved through providing new courses and laboratory training for undergraduate and graduate students, outreach to high school students through the institutions "Engineering Innovation" program, engaging 6th - 8th grade students through the "Science Academy Technology" program in Baltimore and Charles City Middle Schools and broadening the participation of underrepresented groups in the proposed research projects through hands-on research and community outreach.

主要研究者：Gagnon，Zachary R Proposal #：1605553细胞如何感知、响应和朝向或远离外部线索移动是许多生物学和医学现象的核心，包括胚胎发生、形态发生、免疫反应、伤口愈合和癌症转移。趋电性是细胞响应于外部施加的电场而定向偏置其运动的现象，在许多细胞过程中很重要;然而，电场如何影响细胞内细胞骨架组织的潜在物理机制尚不清楚。计划研究的总体目标是确定负责启动细胞趋电性的物理机制。这一目标将通过使用精确的微流体细胞限制室观察趋电迁移和量化电刺激细胞周围的离子活性来实现。智力的优点是基于创新的战略和基本意义，在确定的物理入口点，电场转化为下游的化学信号在细胞趋电性。与传统的侧重于下游信号蛋白的趋电性工作不同，该项目侧重于了解电场对细胞膜的直接影响。 通过为本科生和研究生提供新课程和实验室培训，通过机构的“工程创新”计划向高中生推广，通过巴尔的摩和查尔斯市中学的“科学技术学院”项目吸引6 - 8年级学生，并通过双手扩大代表性不足的群体参与拟议的研究项目-研究和社区外展。细胞如何感知、响应以及走向或远离外部线索对于许多生物和医学现象（包括胚胎发生、形态发生、免疫反应、伤口愈合和癌症转移）至关重要。许多真核细胞具有内部罗盘，使它们能够感知这些线索，通常以化学引诱物，电压或机械应力的梯度形式存在，并将它们的运动偏向特定方向。趋电性是细胞响应于外部施加的电场而定向偏置其运动的现象，在许多细胞过程中很重要;然而，电场如何被转导到细胞中以影响细胞骨架组织的潜在物理机制尚不清楚。该提案的总体目标是确定负责启动细胞趋电性的相关物理机制。这一目标将通过使用精确的微流体细胞限制室观察趋电迁移和量化电刺激细胞周围的离子活性来实现。具体目标是：1）开发和构建微流体限制几何结构，用于在趋电性期间电动离子通量的细胞膜水平分析，2）量化电场诱导的膜过程，包括在趋电性期间的离子流和离子通道活性，以及3）理解下游细胞信号传导如何被这些上游电场诱导的事件激活和转导。计划中的研究的智力价值是基于创新的战略和基本意义，在确定的物理入口点，电场被转换成下游的化学信号在细胞趋电性。与传统的侧重于下游信号蛋白的趋电性工作不同，该项目侧重于了解电场对细胞膜的直接影响。 通过为本科生和研究生提供新课程和实验室培训，通过机构的“工程创新”计划向高中生推广，通过巴尔的摩和查尔斯市中学的“科学技术学院”项目吸引6 - 8年级学生，并通过双手扩大代表性不足的群体参与拟议的研究项目-在研究和社区外展。