CAREER: Mechanotyping Platform for Studies of Soft Biological Matter

加州大学洛杉矶分校被授予开发高通量机械打字平台(MTP)的奖项。细胞和细胞核的机械特性涉及广泛的生物学背景：它们是决定物理力量如何改变基因表达的核心，更广泛地说，它们可以发出信号，表明细胞的生理状态发生了变化--S，例如在恶性转化中。然而，为了促进我们对细胞/核机械性质潜在机制的基本理解，需要探索跨遗传和物理相空间的细胞和核的力学性质；这需要测量大量的样本和单个细胞，这是使用现有方法在可行的时间尺度上无法实现的。MTP在时间、成本和用户可获得性方面比目前的技术有很大改进，由两项独立技术组成：(1)高通量机械筛选(HTMS)仪器可同时探测数百个个体样本的变形性，方法是使它们受到外部应力，迫使它们通过微米级的毛孔变形，并确定传代细胞的数量；这提供了一种生理学相关的分析方法，以检测对细胞在血管系统和组织中的循环和灌流有直接影响的相对力学变化。(2)机械探测系统(MAP)以每秒100的速度直接测量单个细胞和细胞核的弹性模数，方法是让细胞通过微流体通道，用嵌入通道的力探头戳细胞，并确定所产生的变形；这将使以前所未有的速度重复测量单个细胞的机械性能成为可能。这项拟议的研究将建立一个机械分型框架，从干细胞到癌症生物学等领域的生物研究人员都可以使用该框架。探索细胞的机械特征也可以为分类和治疗广泛的疾病提供另一种方法。此外，这项研究将提供对机械表型的分子起源的重要见解，单细胞群体中的异质性，更广泛地说，将通过利用单个细胞的内在质地或机械类型来改变生物学研究中关键信息的搜索。该项目的教育目标是让本科生和高中生以及普通受众参与使用食物和烹饪作为教学工具的科学。用食物传播复杂的科技概念是一种触觉、创新和美味的方式，事实证明，这种方式在促进公众对科学技术的理解方面很受欢迎，也很有效。课程将通过在线模块和互动讲座向高中生群体传播，特别是在科学领域代表性不足的群体。本科生将通过探究驱动的项目，比如设计一个苹果派，在课堂上学习科学。将通过互动活动，包括科学烘焙活动，促进公众对科学的理解。这些教育和外展活动将开创利用食物和烹饪进行多感官科学教育的方法。推广科学和食品知识也解决了美国迫切需要改善社会经济分层社区的饮食和健康问题。欲了解更多信息，请访问www.Scienceandfood.org。

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.