Electro-mechanical coupling directs endothelial activities through intracellular calcium ion deployment

Area of Science:

• Cellular Electrophysiology
• Biomaterials Science
• Mechanobiology

Background:

• Cellular electromechanical coupling is typically unidirectional, except in cardiomyocytes.
• Understanding non-cardiomyocyte responses to electrical stimuli is crucial for regenerative medicine.

Purpose of the Study:

• To investigate the electro-mechanical coupling feedback loop in human umbilical vein endothelial cells (HUVECs).
• To explore the role of Piezo1 channels and calcium dynamics in this process.
• To determine the impact on pre-angiogenic activities and downstream signaling pathways.

Main Methods:

• Culturing HUVECs on patterned piezoelectric materials to generate cellular-scale electric fields.
• Measuring intracellular calcium ion polarization and changes in the built-in electric field.
• Assessing cytoskeletal dynamics and Piezo1 channel activation.
• Analyzing HUVEC alignment, elongation, migration, and eNOS/NO pathway modulation.

Main Results:

• A material-induced external electric field (Eex) triggers an electro-mechanical coupling feedback loop in HUVECs via Piezo1 channels.
• This loop involves polarization of intracellular calcium ions ([Ca2+]i), formation of an opposing internal electric field (Ein), and cytoskeletal changes.
• The feedback loop promotes pre-angiogenic activities like HUVEC alignment, elongation, and migration, modulating the eNOS/NO pathway.

Conclusions:

• Non-cardiomyocytes exhibit a novel electro-mechanical coupling feedback loop initiated by external electric fields.
• This mechanism, involving Piezo1 channels and calcium dynamics, regulates cellular behavior relevant to angiogenesis.
• Findings provide a basis for electrical stimulation-based therapeutic strategies for various diseases.