Multiscale Fractal Shape Cues Support Hierarchical Maturation Of Podocytes Via Curvature induced Extracellular Matrix Patterning

ABSTRACT

Purpose/Objectives: Nature efficiently self-organizes cells and tissues into complex fractal forms. Whether fractal patterning contributes functionally to maturation, and how cells sense and interpret such shape cues, is not well understood. Methodology: Using kidney podocytes as a model system, bioinspired templating of glomerular histology was leveraged to design controlled fractal 21/2 -D surfaces for cell culture. Results: Microcurvature was associated with charge density gradients in space, found to direct extracellular matrix protein organization resulting in hierarchical assembly of cell structures and fractally-branching podocyte morphology in vitro, that was delineated clearly in vitro with a novel highresolution fluorescent assaying technique. Shape stimulation was uniquely associated with development of mature-like foot processes and organized ECM. In applications of drug testing, coronavirus infection, and a cells-as-sensors approach to patient serum diagnostics, fractally stimulated cells were more responsive than flat cultures. Conclusion/Significance: Fractal frameworks may thus provide a functional role in podocyte maturation and could serve to advance other bioengineered systems.