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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 York14260, United States.
In liver cancer, cholesteryl esters (CEs) alter lipid droplet (LD) structure. Increased CE concentration causes rigidification and stiffness, impacting LD mechanical properties.
Area of Science:
- Cell Biology
- Biophysics
- Biochemistry
Background:
- Lipid droplets (LDs) are vital organelles for neutral lipid storage in mammalian cells.
- Liver cancer disrupts LD metabolism, altering their chemical composition and structural integrity.
- Cholesteryl esters (CEs) accumulate in LDs during liver cancer, forming crystalline phases.
Purpose of the Study:
- To investigate the impact of cholesteryl ester (CE) concentration on the structural and mechanical properties of lipid droplets (LDs).
- To understand the link between altered LD composition and their persistence in liver cancer.
Main Methods:
- All-atom molecular dynamics simulations were employed to model LD micropipette aspiration experiments.
- Simulations applied constant surface tension to mimic aspiration, stretching lipid monolayers.
- Analysis focused on partitioning, structural, and mechanical properties under varying CE concentrations.
Main Results:
- Increased CE concentration led to enhanced phospholipid packing within the LD monolayer.
- A nonlinear increase in surface packing defects was observed with rising CE levels.
- LDs exhibited significant rigidification and increased stiffness as CE concentration increased.
Conclusions:
- Cholesteryl ester abundance significantly influences the physical properties of the LD monolayer-core interface.
- These findings enhance understanding of how altered lipid composition affects LD mechanics in liver cancer.
- The study provides insights into the structural basis for undigested LD persistence in liver disease.
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