High Speed Mapping of Mechanical Properties of Tissues

Project Summary / Abstract The immune system is a compelling foundation for precise, potent, and persistent therapies targeting an ever-increasing range of diseases. Adoptive Cellular Therapy based on T cells as a “living drug”, often in combination with Chimeric Antigen Receptor technologies, now provides long-lasting treatment of multiple hematological cancers. Bringing the success of this approach to solid tumors remains a challenge with high reward but significant barriers. Of these, the mechanical resistance of the tumor microenvironment is emerging as a provocative, intriguing, and ultimately actionable mechanism contributing to the immunosuppression seen in solid tumors. However, the scanning probe methods currently used to map the mechanical properties of tissues limits effective testing and understanding of this phenomenon. To address these technical challenges, we introduce a magnetics-based method for mapping tissue stiffness and viscosity that promises greater speed than atomic force microscopy, the current gold standard. The devices, control systems, and protocols needed for this approach will be developed in Specific Aim 1 and validated using well-characterized model systems. This platform will then be used on tissue samples in Specific Aim 2, advancing two strategic applications of these slices. Successful completion of this developmental / exploratory study is a key proof-of- principle of our mapping approach, which will be subsequently applied to reveal the impact of tumor microenvironment mechanics on T cell function. In addition, this platform is immediately applicable to studies investigating additional immune agents, as well as cells central to other healthy and pathological physiologies.