CUSE Biomaterials Seminar: Engineering the Ideal Membrane in vitro Tissue Barrier and Cellular Co-Culture Models

Engineering the Ideal Membrane in vitro Tissue Barrier and Cellular Co-Culture Models

Dr. Tom Gaborski, Associate Professor, Department of Biomedical Engineering, Kate Gleason College of Engineering, Rochester Institute of Technology

Research interest: Nano and microsystems, designing and utilizing nanomembranes for tissue-on-a-chip and biological separations including extracellular vesicle purification and wearable hemodialysis. https://www.rit.edu/directory/trgbme-tom-gaborski

Abstract: Physiologically relevant in vitro tissue barrier and co-culture models are instrumental in investigating the mechanisms of drug delivery, leukocyte transmigration, cancer metastasis, and cell-cell communication during disease progression.Porous substrates are an indispensable part of many barrier model and tissue-on-chip platforms, but are largely treated as just another off-the-shelf component. Our laboratory has developed a variety of ultrathin and optically transparent nano- and micro-porous membranes to better to understand the ideal properties for these systems. We investigated engineering pore size and pore spacing to tune and control cell-substrate and cell-cell interactions. We found that reducing pore-pore spacing generally weakens cell-substrate interactions, as evidenced by fewer focal adhesions and reduced nuclear YAP in endothelial and mesenchymal stem cells, similarly to very soft substrates. On the other hand, endothelial cells on these same membranes have enhanced cell-cell interactions with more robust ZO-1 labeling, confirming a trade-off between cell-cell and cell-substrate interactions during monolayer formation. We further demonstrated that micron and submicron pore size influence early cell-substrate interaction and behavior in terms of migration and the associated extracellular matrix deposition and fibrillogenesis. These results suggest that membrane parameters can be engineered for specific cell types and tissues to promote improved in vitro barrier properties and potentially mimic softer tissue-like substrates.

For Zoom information, please contact Era Jain.