Much remains to be understood about the exact structure-function correlations within the glomerulus, despite detailed mathematical models, micropuncture studies, immunohistochemistry, and ex-vivo perfusion models. A significant barrier to progress is the lack of a tissue culture model for the glomerular slit diaphragm, which is thought to be a critical element of the filtration barrier. Experimental validation of an existing mathematical model of glomerular filtration would provide data regarding the relative contribution of each structure, illuminate understanding of the pathophysiology of glomerular disease, and guide engineering of renal replacement therapy in the future. The advent of Microelectromechanical Systems (MEMS) technology has produced practical surface and bulk micromachining techniques with the ability to manufacture mechanical devices, such as pores, with feature sizes on the same order of magnitude as subcellular structures. A silicon nanofilter with pores the same size as the glomerular slit diaphragm has recently been tested. This project will assemble a model system comprising a nanoporous membrane (NM) closely resembling the slit diaphragms of the glomerulus, and a basement membrane. First, the hydraulic permeability (HP) and sieving coefficients (s) of the NM will be measured by standard means. Second, a podocyte cell line will be grown on NM and a basement membrane (PBM) deposited on the NM, and the podocytes removed. Immunohistochemical staining will be used to verify presence of ECM proteins on the silicon membrane. Third, HP and s will be measured for the NM-PBM membrane. Fourth, data from (1-3) will be compared with existing predictive models of glomerular function.
| Smith, Ross A; Fissell, William H; Fleischman, Aaron J et al. (2012) A low-cost automated streaming potential measurement system. J Lab Autom 17:125-33 |
| Roy, S; Goldman, K; Marchant, R et al. (2011) Implanted renal replacement for end-stage renal disease. Panminerva Med 53:155-66 |
| Kanani, Dharmesh M; Fissell, William H; Roy, Shuvo et al. (2010) Permeability - Selectivity Analysis for Ultrafiltration: Effect of Pore Geometry. J Memb Sci 349:405 |
| Fissell, William H; Hofmann, Christina L; Smith, Ross et al. (2010) Size and conformation of Ficoll as determined by size-exclusion chromatography followed by multiangle light scattering. Am J Physiol Renal Physiol 298:F205-8 |
| Fissell, W H; Humes, H D (2009) New insights into mechanisms of glomerular permselectivity. Minerva Urol Nefrol 61:397-410 |
| Fissell, William H; Hofmann, Christina L; Ferrell, Nicholas et al. (2009) Solute partitioning and filtration by extracellular matrices. Am J Physiol Renal Physiol 297:F1092-100 |
| Fissell, William H; Dubnisheva, Anna; Eldridge, Abigail N et al. (2009) High-Performance Silicon Nanopore Hemofiltration Membranes. J Memb Sci 326:58-63 |
| Fissell, William H; Roy, Shuvo (2009) The implantable artificial kidney. Semin Dial 22:665-70 |
