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Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
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Assembly of the Lipid Bilayer in the ER01:28

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Overview of Fatty Acid Metabolism01:28

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Cholesteryl Esters Modulate Lipid Droplet Rigidity and Monolayer Organization during Liver Cancer Progression.

Oluwatoyin Campbell1, Cecilia Leal2, Viviana Monje1

  • 1Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York, 14260, USA.

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Liver cancer alters lipid droplet (LD) structure, increasing cholesteryl ester (CE) concentration. This leads to rigidification and stiffness of LDs, impacting their mechanical properties during disease progression.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Biochemistry

Background:

  • Lipid droplets (LDs) maintain integrity via lipid monolayers and store neutral lipids.
  • Liver cancer disrupts LD metabolism, altering lipid composition and structural behavior.
  • Increased cholesteryl ester (CE) concentration in LDs is linked to crystalline phase formation in liver cancer.

Purpose of the Study:

  • To investigate the effect of cholesteryl ester (CE) concentration on the partitioning, structural, and mechanical properties of lipid droplets (LDs).
  • To model LD micropipette aspiration experiments using all-atom molecular dynamics simulations.
  • To understand the link between CE concentration, LD structure, and persistence in liver cancer.

Main Methods:

  • All-atom molecular dynamics simulations.
  • Modeling of micropipette aspiration experiments by applying constant lateral surface tension.
  • Analysis of lipid packing, structural defects, and mechanical properties.

Main Results:

  • Increased CE concentration leads to enhanced phospholipid packing within the LD monolayer.
  • CE fatty tail insertion into the monolayer increases phospholipid packing.
  • Elevated CE concentration induces non-linear changes in surface packing defects, resulting in notable rigidification and stiffness of LDs.

Conclusions:

  • Insights into the physical properties at the LD monolayer-core interface during liver cancer progression.
  • Understanding how CE concentration influences LD structural and mechanical behavior.
  • Potential implications for understanding undigested LD persistence in liver cancer patients.