Related Experiment Video
Updated: Jan 30, 2026
Author Spotlight: Evaluation of Lipid Droplet Size and Fusion in Bovine Hepatic Cells
Published on: March 10, 2023
Lipid droplets are rigid and physically suppress phagocytosis, unless cell compression or stretching activates
Michael P Tobin1,2, Irena L Ivanovska1, Steven H Phan1,3
1Molecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104.
Abstract:
As with many cell types, macrophages are sometimes filled with micron-sized lipid droplets (LD's), but effects on phagocytosis of other cells, particulates, and microbes remain unclear. Here, we show that LDs restructure the cytoskeleton but remain round, consistent with a high interfacial tension; functionally, LD's impair actomyosin-driven uptake, which proves independent of target size. Engulfment of targets starts at the apical surface, but LD's displace apical actomyosin to the basal cortex. Partial rescue occurs tissue-relevant compressive stresses which activate actomyosin. Macrophages that are densely filled with LD's or pre-engulfed rigid beads likewise activate actomyosin, which again rescues phagocytosis relative to sparsely loaded cells. As further evidence of LD rigidity, both LD's and rigid beads impede macrophage migration through small pores, and LD's pressed into a nucleus cause rapid focal rupture independent of actin. LD rigidity thus disrupts cytoskeleton organization and nucleus integrity, suppressing motility processes unless actomyosin is activated by cell compression or stretching.
Insights
Lipid droplets (LDs) in macrophages disrupt cell functions like phagocytosis and migration by altering the cytoskeleton. However, mechanical stress can activate actomyosin, rescuing these essential cellular processes.
Area of Science:
- Cell Biology
- Immunology
- Biophysics
Background:
- Macrophages utilize phagocytosis to clear pathogens and cellular debris.
- Lipid droplets (LDs) are intracellular lipid stores found in various cell types, including macrophages.
- The impact of LDs on macrophage phagocytosis and motility remains poorly understood.
Purpose of the Study:
- To investigate the effects of lipid droplets (LDs) on macrophage phagocytosis and migration.
- To determine the role of the cytoskeleton and actomyosin in LD-mediated cellular dysfunction.
- To explore mechanisms for rescuing phagocytosis and motility in LD-loaded macrophages.
Main Methods:
- Cultured macrophages loaded with lipid droplets (LDs).
- Microscopy techniques to visualize cytoskeleton and LDs.
- Assays for phagocytosis of targets and cell migration through pores.
- Application of mechanical stress (compression/stretching) to loaded cells.
Main Results:
- LDs restructure the macrophage cytoskeleton and impair actomyosin-driven phagocytosis.
- LDs displace apical actomyosin, hindering initial engulfment.
- Compressive or stretching stress activates actomyosin, rescuing phagocytosis.
- LDs impede macrophage migration through small pores.
- Nuclear rupture can occur when LDs are pressed into the nucleus.
Conclusions:
- Lipid droplets disrupt macrophage cytoskeleton organization, phagocytosis, and migration.
- Actomyosin activation via mechanical stress can restore these functions.
- LDs pose a threat to nuclear integrity under specific conditions.
Related Concept Videos
00:41Phagocytosis
00:41Phagocytosis
The objective of phagocytosis is often destruction. Cells use phagocytosis to eliminate unwelcome visitors, like pathogens (e.g., viruses and bacteria). Many immune system cells,...
01:06Lipid Digestion
01:17Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...
01:38What are Lipids?
03:38Structure of Lipids