Human Aquaporin 4 Gating Dynamics under Perpendicularly-Oriented Electric-Field Impulses: A Molecular Dynamics Study

Area of Science:

• Biophysics
• Computational Biology
• Molecular Physiology

Background:

• Human aquaporin 4 (AQP4) facilitates water transport across cell membranes.
• Understanding AQP4's gating mechanism is crucial for cellular hydration and fluid balance.
• External stimuli, like electric fields, may modulate AQP4 channel activity.

Purpose of the Study:

• To investigate the effect of external static electric fields on human aquaporin 4 water permeability.
• To analyze the molecular dynamics and dipolar response of AQP4 residues under electric field stress.

Main Methods:

• Molecular dynamics (MD) simulations were employed.
• Simulations were conducted in the absence and presence of electric field pulses (10 ns duration, 0.012-0.065 V/Å intensity).
• Electric fields were applied perpendicular to the pore axis, analyzing water permeability and residue dipolar response.

Main Results:

• Orthogonally-oriented electric field impulses reduced water osmotic permeability through AQP4 channels.
• This reduction correlated with enhanced "dipolar flipping" of key residues, including Serine 211, Histidine 201, Arginine 216, Histidine 95, and Cysteine 178.
• These affected residues are located at both the extracellular and cytoplasmic ends of the pore, influencing the gating mechanism.

Conclusions:

• External static electric fields can modulate human aquaporin 4 water transport.
• The observed decrease in permeability is attributed to electric field-induced conformational changes in critical gating residues.
• These findings provide insights into the electro-mechanical coupling governing aquaporin function.