Probing and modeling cell-cell communication in 2D biomimetic tissues

TL;DR

This study combines experimental biomimetic 2D tissue models with theoretical modeling to understand how cell-cell communication occurs via gap junction-like channels, revealing the physical mechanisms of molecular transport.

Contribution

It introduces a simplified 2D biomimetic tissue model using droplet networks and couples it with a theoretical model to analyze transport mechanisms.

Findings

Diffusion of calcein across DIB networks is characterized.

Transport dynamics are modeled with a Continuous Time Random Walk.

Pore monomer concentration affects waiting times nonlinearly.

Abstract

In tissues, cells in direct physical contact with each other can exchange ions or molecules via protein clusters called gap junctions that form channels across the membranes of adjacent cells. Here, we use a simplified biomimetic approach, coupled with theoretical modeling, to unravel the physical mechanisms controlling such transport. Tissues are mimicked with 2D hexagonal networks of monodisperse aqueous droplets connected by lipid membranes called Droplet Interface Bilayers (DIBs), decorated with $\alpha$-Hemolysin ($\alpha$HL) transmembrane proteins forming nanopores through heptamerization in the membrane. The diffusion of calcein across 2D DIB networks is thoroughly studied using epifluorescence microscopy at various $\alpha$HL concentrations. The results are successfully confronted with a Continuous Time Random Walk model in hexagonal networks, with an average waiting time increasing nonlinearly with the concentration of pore monomers.