Engineering Cell-Substrate Interactions on Porous Membranes to Create Physiologically Relevant Model Systems - Abstract A significant shift is underway in many fields of biomedical research that are rapidly adopting microphysiological systems, also known as tissue chips. Microphysiological systems are being used by biomedical scientists for drug and toxicity testing, disease modeling, and to answer fundamental questions about cell-cell interactions in complex, but tightly controlled environments that can be parallelized for high throughput studies, often with high-resolution microscopy and other real-time readouts. In some studies, induced pluripotent stem cells (iPSCs) allow patient-specific models of drug testing, offering physiological relevance that cannot be matched by any animal model. A central component of nearly all microphysiological systems is the semi-permeable synthetic membrane that facilities co-culture or establishment of a tissue barrier model. This membrane serves to compartmentalize cells or microenvironments while also selectively allowing some species and even cells to transit or transmigrate, typically based simply on a pore size cut-off. While pore size is important for controlling communication between compartments or opposing sides of a barrier model, the membrane also serves as a support scaffold and culture substrate of nearly all cells involved in the system. The overall vision of this MIRA research program is to answer key questions in two interrelated domains: Improve the Understanding of Biological Mechanisms of Cell-Substrate Interactions on Porous Materials, and Advance Ultrathin Membrane Development and Engineer the Ideal Membrane for Physiologically Relevant Tissue Barrier and Co-Culture Models. For the next five years, this research program is focused on building upon my laboratory’s expertise in cell-substrate interactions and materials engineering, and evolving from biophysically focused analysis to understanding the molecular and signaling pathways that are likely driving cellular behaviors with the goal of engineering advanced membranes for more physiologically relevant tissue barrier models. Additionally, my laboratory seeks to move toward an understanding of the dynamics and equilibrium of cell-substrate interactions, particularly in the context of the transition between healthy and disease states in these microphysiological systems.
