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

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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.