In vitro physiological membrane‐on‐a‐chip and its application in cell and neuronal biology

Abstract

Experimental setups to produce and to monitor model membranes have been successfully used for decades and brought invaluable insights into many areas of biology. However, they all have limitations that prevent the full in vitro mimicking and monitoring of most biological processes. Here, a horizontal free‐standing membrane having a physiological lipid composition is reconstituted in a 3D printing‐based microfluidic chip. Simultaneous monitoring of the membrane processes with a microscope and patch‐clamp amplifier reveals that the membrane is free‐standing, horizontal, fully fluid, stable, flat, and large enough. Dual open‐channels adjacent to the bilayer are freely used to alter each lipid monolayer composition (e.g., to form an asymmetric membrane) and oriented protein insertion. Currently, this in vitro membrane setup is integrated to investigate various molecular mechanisms in cell and neuronal biology. I will introduce the application of this setup to decipher the post‐translational insertion of tail‐anchored protein into the ER membrane, including the neuronal vesicle trafficking and α‐synucleinopathies.