The precise spatial organization of neural cells into two-dimensional networks or three-dimensional spheroids is crucial for advancing neuroscience research and drug discoveries, yet remains challenging with conventional, single-function coatings. Here, we propose a programmable bifunctional peptide that integrates a silica-binding domain with a tunable cell-adhesive Arginine-Glycine-Aspartate (RGD) tripeptide. By systematically improving the RGD variant and linker rigidity, we introduced a single coating material that enables on-demand switching between two distinct functions: guiding the patterned growth of functional neural circuits on glass and facilitating the high-throughput formation of uniform neural sp... More
The precise spatial organization of neural cells into two-dimensional networks or three-dimensional spheroids is crucial for advancing neuroscience research and drug discoveries, yet remains challenging with conventional, single-function coatings. Here, we propose a programmable bifunctional peptide that integrates a silica-binding domain with a tunable cell-adhesive Arginine-Glycine-Aspartate (RGD) tripeptide. By systematically improving the RGD variant and linker rigidity, we introduced a single coating material that enables on-demand switching between two distinct functions: guiding the patterned growth of functional neural circuits on glass and facilitating the high-throughput formation of uniform neural spheroids. The latter exhibited high viability, extensive neurite outgrowth, and spontaneous electrophysiological activity, which validates their functional maturity. We establish by this work a versatile and reliable platform for advanced neural interface research, with significant potential for drug discovery and disease modeling.Graphical abstractSupplementary Information The online version contains supplementary material available at 10.1186/s12951-026-04032-x.
