BRITE Pivot: Transforming Mechanobiology - Integrating Spatial Transcriptomics, Collagen Architecture, and Tissue Mechanics

This BRITE Pivot research project aims to develop new engineering tools to better understand how biological signals (like gene and protein expression) interact with mechanical signals (like tissue structure and stiffness) in the body. These tools will allow scientists to combine and visualize biological and mechanical data at the cellular and subcellular levels, offering new mechanobiology insights into how these signals work together. The research focuses on the uterus, specifically investigating how exposure to endocrine-disrupting chemicals (EDCs), such as propylparaben (PP)—a common preservative found in everyday products like lotions and cosmetics—may affect fertility and pregnancy. Growing evidence suggests that long-term exposure to EDCs may trigger inflammation and fibrosis (the buildup of collagen), which can interfere with embryo implantation, a crucial step in pregnancy. Tools that look to be developed could also be used to study inflammation and fibrosis in other organs, including the lung, kidney, and liver. By advancing engineering tools and applying them to urgent public health challenges, this research seeks to advance the fields of mechanobiology and mechanics and contributes more broadly to understanding tissue dysfunction across multiple organ systems. This research aims to bring powerful and emerging tools in molecular and cellular biology—spatial omics and multiplexed protein profiling—into the field of mechanobiology. The goal is to integrate and co-register these complex biological data with mechanical and imaging data obtained by second harmonic generation (SHG), atomic force microscopy (AFM), and nanoindentation. This effort seeks to create a new multi-scale framework for understanding mechanobiology by mapping spatial relationships among molecular signals, tissue microstructure (e.g., collagen fiber organization), and mechanical properties at cellular and subcellular resolution. The project focuses on uterine tissue, which exhibits complex signaling and remodeling, to investigate how exposure to endocrine-disrupting chemicals (EDCs), specifically propylparaben (PP), alters tissue structure and mechanics. While the uterus serves to set up the framework, the experimental and computational approaches that look to be developed can be broadly applicable to other heterogeneous tissues influenced by mechanical and molecular disruption, such as the lung, liver, and kidney. 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.