Ultra-thin and ultra-porous nanofiber networks as a basement-membrane mimic

Current basement membrane (BM) mimics used for modeling endothelial and epithelial barriers in vitro do not faithfully recapitulate key in vivo physiological properties such as BM thickness, porosity, stiffness, and fibrous composition. Here, we use networks of precisely arranged nanofibers to form ultra-thin (similar to 3 mu m thick) and ultra-porous (similar to 90%) BM mimics for blood-brain barrier modeling. We show that these nanofiber networks enable close contact between endothelial monolayers and pericytes across the membrane, which are known to regulate barrier tightness. Cytoskeletal staining and transendothelial electrical resistance (TEER) measurements reveal barrier formation on nanofiber membranes integrated within microfluidic devices and transwell inserts. Further, significantly higher TEER values indicate a biological benefit for co-cultures formed on the ultra-thin nanofiber membranes. Our BM mimic overcomes critical technological challenges in forming co-cultures that are in proximity and facilitate cell-cell contact, while still being constrained to their respective sides. We anticipate that our nanofiber networks will find applications in drug discovery, cell migration, and barrier dysfunction studies.

Automated summary

Ultra-thin and ultra-porous basement membrane mimics using precisely arranged nanofiber networks are developed for blood-brain barrier modeling. The nanofiber networks enable close contact between endothelial monolayers and pericytes, regulating barrier tightness. Co-cultures on the ultra-thin nanofiber membranes show higher transendothelial electrical resistance values, indicating a biological benefit.