CAREER: Mechanotyping Platform for Studies of Soft Biological Matter

职业：软生物物质研究的机械分型平台

• 批准号: 1254185
• 负责人: Amy Rowat
• 金额: $ 61.41万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1254185&HistoricalAwards=false
• 关键词: CAREER; Mechanotyping; Platform; Studies; Soft

An award is made to UCLA to develop a high throughput Mechanotyping Platform (MTP). Mechanical properties of cells and nuclei are implicated in a wide range of biological contexts: they are central for determining how physical forces alter gene expression, and more broadly they can signal a transformation in a cell?s physiological state, such as in malignant transformation. However, to advance our fundamental understanding of the mechanisms underlying cell/nuclear mechanical properties requires probing the mechanical properties of cells and nuclei across genetic and physical phase space; this demands measurements of a large number of samples and single cells which cannot be achieved on a feasible timescale using existing methods. MTP offers dramatic improvements over current techniques in time, cost, and user-accessibility, and is comprised of two independent technologies: (1) High Throughput Mechanical Screening (HTMS) instrumentation simultaneously probes the deformability of hundreds of individual samples by subjecting them to external stresses, forcing them to deform through micron-scale pores, and determining the number of passaged cells; this provides a physiologically relevant assay to detect relative mechanical changes that have direct implications for the circulation and perfusion of cells through vasculature and tissues. (2) A Mechanical Probing System (MaPS) measures elastic moduli directly from single cells and nuclei at rates of 100 per second by flowing cells through a microfluidic channel, poking the cell with a force probe embedded in the channel, and determining the resultant deformation; this will enable reproducible measurements of the mechanical properties of single cells at unprecedented speeds. The proposed research will establish a framework for mechanotyping that will be accessible to biological researchers in fields ranging from stem cells to cancer biology. Probing the mechanical signatures of cells can also provide an alternative approach to classify and treat a wide range of diseases. In addition, this research will provide critical insight into the molecular origins of mechanical phenotype, heterogeneity within a population of single cells, and more broadly, will transform the search for crucial information in biological research by exploiting the inherent texture or mechanotype of individual cells.The educational objective of this project is to engage undergraduate and high school students, as well as general audiences, in science using food and cooking as pedagogical tools. Communicating sophisticated scientific and technological concepts using food is a tactile, innovative, and tasty approach that is proving to be popular and effective in promoting the public understanding of science and technology. Curricula will be disseminated through online modules and interactive lectures to populations of high school students, especially groups underrepresented in science. Undergraduate students will be engaged in learning science in a classroom setting through inquiry-driven projects, such as engineering an apple pie. The public understanding of science will be promoted through interactive events, including a Scientific Bake-off. These education and outreach activities will pioneer methodologies in multisensoryscience education using food and cooking. Promoting knowledge of science and food also addresses America's pressing need to improve eating and health issues for socio-economically-stratified communities. More information is available at www.scienceandfood.org.

授予加州大学洛杉矶分校开发高通量机械分型平台（MTP）。细胞和细胞核的力学性质涉及广泛的生物学背景：它们是决定物理力如何改变基因表达的核心，更广泛地说，它们可以发出细胞转化的信号。的生理状态，如在恶性转化。然而，为了推进我们对细胞/核机械特性的基本机制的理解，需要探测细胞和核在遗传和物理相空间中的机械特性;这需要测量大量的样品和单细胞，这在可行的时间尺度上无法使用现有方法实现。MTP在时间、成本和用户可及性方面提供了比当前技术显著的改进，并且由两种独立的技术组成：（1）高重复机械筛选（HTMS）仪器同时探测数百个个体样品的可变形性，其通过使它们经受外部应力，迫使它们变形通过微米级孔，并确定传代细胞的数量;这提供了一种生理学相关的测定，以检测对细胞通过脉管系统和组织的循环和灌注具有直接影响的相对机械变化。(2)机械探针系统（MaPS）通过使细胞流过微流体通道，用嵌入通道中的力探针戳细胞，并确定所产生的变形，以每秒100的速率直接从单细胞和细胞核测量弹性模量;这将使单细胞的机械特性的可重复测量以前所未有的速度进行。这项拟议中的研究将建立一个机械分型的框架，使从干细胞到癌症生物学等领域的生物研究人员都能使用。探测细胞的机械特征也可以提供一种分类和治疗各种疾病的替代方法。此外，这项研究将提供关键的洞察力的分子起源的机械表型，异质性在一个人口的单细胞，更广泛地说，将改变搜索的关键信息在生物学研究中，通过利用固有的纹理或mechanotype个别细胞。在科学中使用食物和烹饪作为教学工具。用食物传达复杂的科学和技术概念是一种触觉，创新和美味的方法，被证明是流行的，有效地促进公众对科学和技术的理解。课程将通过在线模块和互动讲座向高中生群体，特别是在科学方面代表性不足的群体传播。本科生将通过探究驱动的项目（如设计苹果派）在课堂环境中学习科学。将通过互动活动促进公众对科学的理解，包括科学烘焙比赛。这些教育和推广活动将开创利用食物和烹饪进行多感官科学教育的方法。促进科学和食品知识还可以解决美国改善社会经济分层社区饮食和健康问题的迫切需要。更多信息见www.scienceandfood.org。