BRITE Pivot: Molecular Basis of Mechanotransduction Probed Using Soft Materials Science

组织的变形是触觉、疼痛、胃中食物量以及肠道如何工作的基础。检测变形对其他器官和组织的健康功能也很重要，例如血管直径如何控制血压。所有这些功能都取决于细胞的变形如何改变它们的行为。触觉和内部变形的正常功能是我们每时每刻的体验和生活质量的基础，触觉或变形感觉的中断会导致疾病。在这个项目中，我们将使用几乎原子大小的力传感器来了解一种细胞对变形的反应。这些细胞使用一种称为PIEZO的蛋白质，它将变形转化为细胞的生物信号。这个促进工程学变革和公平进步的研究思路（BRITE）Pivot项目的目标是了解与变形的内部感觉相关的人类触觉和功能障碍。该项目包括扩大STEM教育机会的坚定承诺。首席研究员是加州大学圣地亚哥分校IDEA工程学生中心的主任，该中心通过20多个项目为大约8000名学生提供服务。这个BRITE Pivot项目将利用以前在纳米结构薄膜机电性能方面的工作，走向一个新的研究领域。也就是说，机电活性材料在工程结构中的应用，以探测分子和细胞机械转导中的问题。为了在这一跨学科领域取得进展，首席研究员将在Patapoutian教授的实验室进行为期3个月的居住休假，Patapoutian教授发现了无处不在的机械响应孔形成蛋白PIEZO家族。在三个相互关联但独立的任务中，联合收割机将分子生物学中的这种新技能与现有技能相结合，他的实验室将建立新型微流体和纳米材料传感器来测量（1）含有PIEZO的细胞的机械特性，（2）细胞的激活阈值作为PIEZO表达和激活程度的函数，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Deformation of tissue is fundamental to the senses of touch, and pain, the amount of food in the stomach, and to how the intestines work. Detecting deformation also is important to the healthy function of other organs and tissues such as how blood vessel diameter controls blood pressure. All these functions depend upon how deformation of cells changes their behavior. The normal functioning of touch and internal deformation are the basis of our moment-to-moment experience and quality of life, and disruption of touch or deformation sensation causes disease. In this project, we will use nearly atomic sized force sensors to understand the behavior of a type of cells that respond to deformation. These cells use a type of protein, called a PIEZO, which converts deformation into a biological signal for the cell. The goal of this Boosting Research Ideas for Transformative and Equitable Advances in Engineering (BRITE) Pivot project is to understand human touch and dysfunctions associated with the internal sensation of deformation. The project includes a strong commitment to broadening access to STEM education. The principal investigator is the Faculty Director of the IDEA Engineering Student Center at UC San Diego, which serves approximately 8000 students through more than twenty programs.This BRITE Pivot project will leverage previous work in the electromechanical properties of nanostructured thin films toward a new area of research. That is, the application of electromechanically active materials in engineered constructs to probe questions in molecular and cellular mechanotransduction. To make progress in this interdisciplinary area, the principal investigator will conduct an annual 3-month sabbatical-in-residence in the laboratory of Prof. Patapoutian, who discovered the ubiquitous PIEZO family of mechanically responsive pore-forming proteins. In three interrelated but independent tasks that combine this new skill in molecular biology with existing skills, his laboratory will build novel microfluidic and nanomaterial-based sensors to measure (1) the mechanical properties of PIEZO-containing cells, (2) the activation thresholds of cells as a function of PIEZO expression and extent of activation, and to understand (3) cellular mechanisms for tactile sensation in humans.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.