Integrin β1 Bridges ECM Microfibers and Intracellular Amino Acid Variations in Liver Cells

Description:
Although numerous recent studies have shown the importance of polymeric microfibrous extracellular matrices (ECMs) in maintaining cell behaviors and functions, the mechanistic nexus between ECMs and intracellular activities is largely unknown. Therefore, we present our findings that ECM microstructures could regulate intracellular amino acid levels in liver cells mechanistically through integrin ß1 (IGTß1). Two ECM conditions, flat and microfibrous, were prepared and studied. In addition to characterizing cell growth, albumin production, urea synthesis, and cytochrome p450 activity, we found that the microfibrous ECM generally upregulated the intracellular amino acid levels. Further explorations showed that cells on the flat substrate expressed more integrin ß1 than cells on the microfibers. Moreover, after partially blocking integrin ß1 in cells on the flat substrate, the intracellular amino acid levels were restored, strongly supporting integrin ß1 as the linking
mechanism.

Speaker: John Terrell - UMBC
I am a fourth year graduate student in Dr. Chengpeng Chen's lab at UMBC in Baltimore, MD. It has been well established that commonly used in vitro cell models, such as culture flasks or other flat-bottomed plastic systems, are insufficient for maintaining proper cell function. One clear piece of evidence regarding this is the loss of primary human hepatocyte (liver parenchymal cell) phenotype and function within 24-48 hours when seeded on a standard culture flask, but functions are retained for up to several weeks when cultured in a 3D environment. My research investigates multi-omics differences in hepatocytes grown in 2D and 3D environments to understand what effects surface topography has on the cell. Further on we will characterize how information from the cell culture surface is mechanistically transduced to the cell to cause these differences.