Multiscale fractal shape cues support hierarchical assembly and maturation of podocytes via curvature-induced extracellular matrix patterning

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. Using kidney podocytes as a model system, bioinspired templating of glomerular histology was leveraged to design controlled fractal 2½ -D surfaces for cell culture. 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, outlined with a novel fluorescent assaying technique. Shape simulation was uniquely associated with mature-like foot processes on an 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. Fractal frameworks may thus provide a functional role in podocyte maturation and could serve to advance other bioengineered systems. Biomimetic fractal topography modulates charge density gradients to orchestrate cell attachment and drive development.