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Biomechanics of cultured hepatic cells during different steatogenic hits. | LitMetric

Biomechanics of cultured hepatic cells during different steatogenic hits.

J Mech Behav Biomed Mater

Department of Earth, Environment and Life Sciences (DISTAV), University of Genova, Corso Europa 26, 16132, Genova, Italy. Electronic address:

Published: September 2019

AI Article Synopsis

  • Non-alcoholic fatty liver disease (NAFLD) is linked to overnutrition and characterized by different types of fat accumulation in liver cells, which affects their function and stiffness.
  • Research used in vitro models to study how various combinations of fructose, fatty acids, and tumor necrosis factor (TNF)α impact lipid droplet characteristics and the mechanical properties of hepatocytes.
  • Results revealed that the size and number of lipid droplets significantly affect cell stiffness and shape, indicating that understanding these mechanics could lead to new insights in treating NAFLD.

Article Abstract

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease often associated with overnutrition. Number and morphometry of lipid droplets (LDs) define micro vs macrovesicular steatosis, influence the morphology and function of hepatocytes and possibly their stiffness. The link between grade and features of steatosis and biomechanical properties of single hepatocytes requires deeper investigations. In vitro NAFLD models with distinct steatosis conditions were set by exposing FaO hepatoma cells to single or combined fructose (Fru), fatty acids (FA), and tumor necrosis factor (TNF)α. Single Cell Force Spectroscopy and Quantitative Phase Microscopy quantified the single cell stiffness and a series of morphometric parameters; the mRNA expression of genes involved in lipid metabolism was quantified by real-time PCR. In our models, LD size and number increased with Fru and FA as single agents, and more with combined Fru/FA (macrovesicular steatosis), while FA/TNFα combination increased LD number with a reduction in their size (microvesicular steatosis). We found that the changes in LD size and number influenced cell stiffness and morphometry as follows: (i) single cell elasticity increased in macrovesicular steatosis (maximally with combined Fru/FA); (ii) FA-induced steatosis resulted in cells thinner and larger, whereas combined FA/TNFα shrunk the hepatocytes. Taken together the data on hepatocyte biomechanics show that, in addition to extent of lipid accumulation, cell stiffness is mainly influenced by LD size, while cell morphometry directly relates to LD number. Our findings suggest that a novel mechanobiology perspective might provide future contributions in NAFLD research.

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Source
http://dx.doi.org/10.1016/j.jmbbm.2019.05.036DOI Listing

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