(10/13) Dr. Chengpeng Chen

Dr. Chengpeng Chen

Department of Chemistry/Biochemistry

Friday, October 13, 2023
12:00 Noon
Room 120 – Meyerhoff Chemistry Building

3D-Printed Modular and Scalable Microfluidics to Investigate ECM’s Roles in Modulating Cell Metabolome

Microfluidic tissue models have rapidly evolved with applications from basic research to pharmaceutical screenings. Recently, protocols to include 3D extracellular matrices (ECMs) have emerged to mimic native cell microenvironments. Nonetheless, 3D ECMs’ roles in mediating cell functions remain largely elusive, especially from molecular perspectives. My laboratory started a new direction that explores the interactions between 3D ECMs and metabolome. Metabolites and their concentrations are direct effectors of cellular machinery, and thus, metabolomic profiling can provide a holistic picture of cell functions. Here, we first present an unprecedented microfluidic system for endothelium studies. Endothelial cells form the innermost layer of blood vessels (endothelium), which play key roles in the homeostasis of the cardiovascular system and mass transfer between blood and surrounding tissues. The devices were fabricated via 3D printing with robust structures that could sustain flow rates up to 4000 µL/min (covering the whole shear stress range in vivo). In addition, a reservoir device fitting a 12-channel pipette was added to the flows as a “media transfer station”, where extracellular samples could be taken. The cells on 3D ECMs could be removed for immediate quenching and lysis, which is critical for metabolomics studies because metabolites can change rapidly during a sample collection process. Also, the robustness of the devices enabled scaling up twelve parallel experiments. With this platform, we found that the aligned fibrous topography on the inside of human arteries could modulate arginine metabolism in endothelial cells, and thus the production of nitric oxide, a critical molecule controlling vasodilation, inflammation, oxidative stress, etc. On a similar microfluidic platform, we also found for the first time that the ECM microstructures can regulate the energy metabolism in hepatocytes. Further studies reveal the mechanistic role of integrins. These results not only show the necessity to include proper ECM structures in tissue modeling, but also provide new understanding and metabolic targets as potential therapeutic strategies to conquer the various diseases with ECM restructurings, such as fibrosis and sclerosis. After the pandemic, my lab started a new research route to develop wearable and point-of-care sensors for health monitoring. A brief discussion of the technology developments will also be included in the presentation.