DHA-containing phospholipids control membrane fusion and transcellular tunnel dynamics

Area of Science:

• Cell biology
• Biochemistry
• Physiology

Background:

• Polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA), are vital for physiological functions.
• Phospholipids containing DHA (DHA-PLs) play a critical role in cell membrane structure and dynamics.
• Transendothelial cell macroapertures (TEMs) are dynamic structures involved in cell barrier function.

Purpose of the Study:

• To investigate the impact of DHA-PLs on the dynamics of transendothelial cell macroapertures (TEMs).
• To understand how DHA enrichment in the plasma membrane affects endothelial cell biomechanical properties.
• To explore the relationship between DHA-PL levels and the stability and size of TEMs.

Main Methods:

• Lipidomic analysis of human umbilical vein endothelial cells (HUVECs) subjected to a DHA diet.
• Investigation of RhoA inhibition-associated cell spreading and TEM formation.
• Measurement of cell thickness, membrane fusion properties, membrane tension, and cell cortex rigidity.

Main Results:

• A DHA diet led to a 6-fold enrichment of DHA-PLs at the HUVEC plasma membrane, replacing oleic acid-containing PLs (OA-PLs).
• DHA-PL enrichment reduced cell thickness and promoted membrane fusion permissive for TEM initiation.
• Homeostatic control minimized TEM area changes by reducing TEM size and lifetime; low DHA-PL levels resulted in wider, unstable TEMs.

Conclusions:

• Variations in DHA-PL levels significantly alter endothelial cell biomechanical properties.
• DHA-PLs modulate membrane tension and cell cortex rigidity, influencing TEM formation and stability.
• These findings highlight the importance of DHA in maintaining endothelial barrier integrity through regulation of cell membrane properties.