Understanding How Motile Cells Make Decisions When Subject to Multiple Chemical and Physical Cues

了解运动细胞在受到多种化学和物理提示时如何做出决定

• 批准号: 1536616
• 负责人: Lakshminarayana Mahadevan
• 金额: $ 40万
• 依托单位: Harvard University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1536616&HistoricalAwards=false
• 关键词: Understanding; How; Motile; Cells; Make

Cells make behavioral decisions based on measurements of their environment all the time. Chemical cues re-orient cells towards food or sites of infection. Physical cues report on local hydrostatic pressure, cellular crowding, adhesion etc. Together these cues allow a cell to make decisions about its fate (if it is in an embryonic state), move, divide, assemble into a tissue etc. Understanding how cells integrate multiple physico-chemical measurements before making a decision is thus critical in characterizing tissue and organ development, wound healing, cancer metastasis and in controlling cells to create artificial tissues and organs. This award supports research that will combine experimental and theoretical studies to study how a single cell can integrate physical and chemical cues to decide which direction to move in. Since all natural and artificial tissues contain cells, understanding how they make decisions will allow for better control of natural tissues and provide guidelines for creating artificial functional tissues. Thus this research will help society. Furthermore, as the research is highly multi-disciplinary and involves tools and techniques from molecular biology, microscopy, microfluidics on the one hand, and statistical and nonlinear physics, hydrodynamics, and optimization and control theory on the other, it will broaden participation of engineers and scientists from many different group including under-represented minorities and positively impact engineering education by fertilizing different disciplines.Oriented motility of cells in response to external cues is critical in determining the survival of single-celled organisms and the normal development and maintenance of multi-cellular organisms like us. The molecular basis for this orientation has been widely studied but an integrated quantitative model remains elusive, in part due to the absence of controlled quantitative environments. This award will support research to close the gap. Microenvironments that can be programmed with both chemical and physical cues will force neutrophils to crawl through channels they occlude and provide high-resolution images of intracellular signaling for automated data analysis. The ability to quantitatively control the cellular environment and simultaneously measure intracellular signaling will allow for a multi-phase model of cell polarization and motility that accounts for cytoskeletal and membrane dynamics combining statistical mechanics, hydrodynamics and elasticity, while integrating the sensing of the physical (pressure) and chemical (cytokine) environment into a biophysical basis for cellular decision making.

细胞总是根据对环境的测量做出行为决定。 化学信号使细胞重新定位于食物或感染部位。 物理线索报告当地的静水压力，细胞拥挤，粘附等，这些线索一起让一个细胞作出决定，它的命运（如果它处于胚胎状态）、移动、分裂、组装成组织等。因此，了解细胞在做出决定之前如何整合多个物理化学测量对于表征组织和器官发育、伤口愈合、癌症转移和控制细胞以制造人造组织和器官。该奖项支持将联合收割机实验和理论研究相结合的研究，以研究单个细胞如何整合物理和化学线索，以决定向哪个方向移动。由于所有天然和人造组织都含有细胞，因此了解它们如何做出决定将有助于更好地控制天然组织，并为创造人工功能组织提供指导。因此，这项研究将有助于社会。 此外，由于研究是高度多学科的，一方面涉及分子生物学，显微镜，微流体学的工具和技术，另一方面涉及统计和非线性物理学，流体动力学以及优化和控制理论，它将扩大来自许多不同群体工程师和科学家的参与，代表少数民族和积极影响工程教育的不同学科。定向运动的细胞响应外部线索是至关重要的，在决定生存的单一，细胞生物以及像我们这样的多细胞生物的正常发育和维持。 这种取向的分子基础已被广泛研究，但一个完整的定量模型仍然难以捉摸，部分原因是缺乏受控的定量环境。该奖项将支持缩小差距的研究。可以用化学和物理线索编程的微环境将迫使中性粒细胞通过它们堵塞的通道爬行，并为自动数据分析提供细胞内信号的高分辨率图像。定量控制细胞环境并同时测量细胞内信号传导的能力将允许细胞极化和运动的多相模型，其考虑细胞骨架和膜动力学，结合统计力学、流体力学和弹性，同时将物理（压力）和化学（细胞因子）环境的感测整合到细胞决策的生物物理基础中。