Top-down perspectives on cell membrane potential and protein transcription

Area of Science:

• Biophysics
• Developmental Biology
• Systems Biology

Background:

• Existing models often use bottom-up approaches to describe bioelectricity and gene transcription.
• A top-down perspective offers complementary insights into multicellular interactions.

Purpose of the Study:

• To explore a simple model of multicellular interplay between bioelectricity and protein transcription from a top-down perspective.
• To investigate how cell membrane potential influences gene expression states in a multicellular context.

Main Methods:

• Modeling non-excitable cells' bioelectrical representation of their environment, including neighboring cells.
• Utilizing voltage-gated ion channels and intercellular junctions in simulations.
• Analyzing spatio-temporal distributions of signaling ions and molecules influenced by local electric potentials.

Main Results:

• Simulations predict shifts in membrane potential drive transitions between gene expression states.
• Depolarized cells exhibit less effective control over distinct gene expressions compared to polarized cells.
• Community effects enable the extension of single-cell control to the multicellular level.
• Multicellular potentials correlate with distinct downstream gene expression patterns.

Conclusions:

• A central cell can sense neighboring cell count and bioelectrical states via membrane potential changes.
• Multiscale bioelectricity functions as a top-down regulatory mechanism in development and regeneration.
• This top-down model provides novel insights into bioelectrical control of gene expression.