What question did this study set out to answer?

This research aims to explore how different levels of substrate stiffness influence neuronal adhesion and network connectivity in hiPSC-derived neurons.

April 4, 2026Open Access

Substrate Stiffness Modulates Cell-Network Topology in Human-Derived Neurons

Key Points

This research aims to explore how different levels of substrate stiffness influence neuronal adhesion and network connectivity in hiPSC-derived neurons.
Used confocal imaging and network topology analysis to assess neuronal cultures.
Compared soft (∼12 kPa) and stiff (∼1.5 MPa) substrates while matching surface properties.
Analyzed NCAM expression as a measure of neuronal adhesion and outgrowth at 10 DIV.
Higher NCAM levels were found on soft PDMS, indicating better neuronal adhesion.
Soft PDMS demonstrated increased clustering, reduced path length, and greater small-worldness in network topology analysis.

Abstract

Using confocal imaging and network topology analysis, we investigated how substrate stiffness affects adhesion and connectivity in hiPSC-derived neuronal cultures grown on polydimethylsiloxane (PDMS). We compared soft (∼12 kPa) and stiff (∼1.5 MPa) substrates with matched surface properties to isolate mechanical effects. Confocal analysis of NCAM expression revealed higher levels on soft PDMS at 10 DIV, indicating enhanced neuronal adhesion and outgrowth. Network topology analysis showed that only soft PDMS supported increased clustering, reduced path length, and higher small-worldness, reflecting more efficient connectivity. These results underscore the importance of substrate compliance in promoting neuronal development and inform scaffold design for neural engineering.

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Cite This Study

Bruno et al. (Thu,) studied this question.

synapsesocial.com/papers/69d0aeb9659487ece0fa4a79 https://doi.org/https://doi.org/10.1021/acsomega.5c12283

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