Structural evolution of lipid droplets in murine liver cancer

Hepatocellular carcinoma (HCC) is a primary liver cancer that arises from hepatocytes, the main functional cells of the liver. It represents a major global health concern due to its high incidence and often late-stage diagnosis, making it one of the leading causes of cancer-related deaths worldwide. A notable observation in the context of HCC is its shared characteristics with fatty liver disease which is characterized by the accumulation of excess fat in liver cells. As lipid droplets (LDs) are cytosolic fat storage organelles, they have gained increasing recognition for their significant involvement in liver diseases from recent research. However, how LDs manage and pack a surplus of fat during tumorigenesis remains unknown. We conducted a comprehensive study utilizing micropipette aspiration, X-ray scattering, cryo-EM, and lipidomics to elucidate how the morphology, composition, structure, and mechanical properties of LDs evolve during tumorigenesis. Our study discovers that LDs extracted from mice with liver cancer display an unbalanced ratio of cholesterol esters (CEs) to triacylglycerols (TAGs). This imbalance induces an unexpected structural transformation where CEs and TAGs close pack into a multilamellar structure instead of being present in a liquid-like state. This structural evolution is accompanied by a remarkable increase in stiffness seen by a doubling of the area expansivity modulus of LDs compared to those from normal liver tissue. These findings provide valuable insights into the role of LDs’ biophysical properties during liver cancer progression.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Materials Science & Engr

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Li, Lily Xueqi

Contributors dc:contributor

• Leal, Cecilia

• Lipid Droplets
• Cancer
• Triacylglycerols
• Cholesterol Esters

Statement dc:rights

• Copyright 2023 Lily Li

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/122059

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F122059