Characterization of Angiogenesis Assays to Probe Metabolic Profiles of Tip and Stalk Cells
Sabo, Lindsey
0009-0007-5877-3152
:
2024-03-21
Abstract
Angiogenesis is the generation of new blood vessels from existing vasculature and is essential for growth and development of the human body. However, it also plays a role in many pathological processes, such as tumor growth. Angiogenesis is characterized by two distinct endothelial cell phenotypes: tip cells that lead the sprout and stalk cells that follow and proliferate to form the new vessel. It has been previously reported that angiogenesis is highly dependent on the physical properties of the ECM, and denser matrices have been shown to result in increased tip cell metabolism due to increased energetic requirements for cell migration. However, the specific impact of the ECM on the metabolism of the stalk endothelial subtype is not well known. Stalk cells have been shown to interact with the ECM to a lesser degree than tip cells and are not thought to play a large role in cell migration, so we hypothesized the difference in tip and stalk metabolism would increase with matrix density. To investigate this, we first characterized and compared the spheroid and microbead models of angiogenesis to ensure that the optimal model was used for the subsequent investigation. The spheroid assay was selected for this analysis because it produced increased angiogenic output and longer strands that were ideal for studying cell-cell interactions. Unexpectedly, we found no significant difference in tip-stalk metabolism in different matrix densities. This could suggest that stalk cells are able to adapt their metabolism in response to matrix density changes and could interact with the ECM to a higher degree than previously thought.