Effects of Lipid Deposition on Viscoelastic Response in Human Hepatic Cell Line HepG2

Abstract

Hepatic steatosis is associated with various liver diseases. The main pathological feature of steatosis is the excessive lipid accumulation. Ultrasound has been extensively used for the diagnosis of hepatic steatosis. However, most ultrasound-based non-invasive methods are still not accurate enough for cases with light lipid infiltration. One important reason is that the extent to which lipid infiltration may affect mechanical properties of hepatocytes remains unknown. In this work, we used atomic force microscope and in vitro dose-dependent lipid deposition model to detect the quantitative changes of mechanical properties under different degrees of steatosis in a single-cell level. The results show that hepatic cells with lipid deposition can be treated as linear viscoelastic materials with the power law creep compliance and relaxation modulus. Further analysis showed that even slight accumulation of lipid can lead to measurable decrease of stiffness and increased fluidity in liver cells. The accurate detection of viscoelastic properties of hepatocytes and the analysis methods may provide novel insights into hepatic steatosis grading, especially in the very early stage with reversible liver lesion. The application of viscoelasticity index for grading fat deposition might be a new detection indicator in future clinical diagnosis.

Mechanobiology in the development and progression of non-alcoholic fatty liver disease: an updated review

“…Deficiencies of various enzymes and structural proteins involved in the formation, expansion, and degradation of LDs have been implicated in hepatocellular fat accumulation, which may manifest as macrovesicular steatosis (characterized by one or more large LDs displacing the nucleus) or microvesicular steatosis (characterized by the presence of numerous small LDs that do not displace the nucleus) [50] . Genetic variants associated with increased risk of NAFLD have been identified for perilipin 2 (PLIN2), which helps to stabilize LDs and inhibit autophagy of growing LDs [51] ; for the patatin-like phospholipase domain-containing protein 3 (PNPLA3), which helps to remove triacylglycerols from the LD core and facilitate the proteasomal degradation of LDs [52] ; and for the protein product of transmembrane 6 family member 2 (TM6SF2), which is normally involved in the secretion of triacylglycerol-rich lipoproteins [53] . The biology of LDs and their involvement in the pathophysiology of NAFLD have been summarized in several recent and excellent reviews [13][14][15] .…”