Extracellular Matrix Microstructures Modulate Hepatic Methionine Cycle and Methylations

Abstract

The field of mechanobiology has grown in the past decade, but limited studies investigate how the extracellular matrix affects the cell metabolome. The methionine cycle involves the catabolism and regeneration of methionine through the donation and recovery of a single methyl group; this methyl group can methylate DNA, RNA, and proteins to alter gene expression and protein–protein interactions. Through studying cells cultured on fibrous (mimicking healthy extracellular matrice (ECM)) and flat (mimicking severely fibrotic ECM) substrates, we observed an increase in methionine cycle enzyme expression in cells on the flat substrate. We also present how the methionine cycle is modulated by the ECM through transmembrane protein integrin β1. By inhibiting integrin activation through the ligand-mimicking peptide RGD, we observed that the methionine cycle was protected from alteration. The results presented provide insight into possible therapeutic targets for fibrotic diseases and knowledge of mechanisms by which the ECM alters cell processes.