Protein-to-Tissue Model of Glomerular Mechanobiology

The research objective of this award is to use computational models at different length scales to develop an understanding of how changes to the proteins that form the glomerular basement membrane (GBM) of the kidney alter the mechanical properties of the basement membrane as a whole. The GBM is the major structural layer of the filtration apparatus of the kidney, so its ability to withstand high pressures and allow blood plasma to pass through it is necessary for proper kidney function. A series of models from the molecular to the tissue scale will be constructed and linked together. The stiffness and strength of the tissue will be estimated based on the protein properties, as will the permeability of the tissue (i.e., its tendency to permit filtration flow through it). Finally, changes in the properties of the tissue, coupled with the known demand for filtration, will be used to model dynamic changes in the GBM in response to changes in load or protein properties.

If successful, these studies will help explain how the kidney, which filters 40-50 gallons of blood every day, performs in healthy conditions and suffers decreased performance in disease. The new understanding may help drive treatments for patients with genetic diseases that affect the kidney (e.g., Alport syndrome) and also for patients with kidney disease arising from other sources, such as diabetes. The project also involves training of a Ph.D. student in biomedical engineering and an outreach program for students interested in STEM at the College of the Menominee Nation, which will contribute to the strength and diversity of our high-tech workforce.