Researchers create a magnetic nanoscale system that reversibly switches groove and ridge structures to regulate stem cell adhesion and differentiation.
(Nanowerk Spotlight) Tissue regeneration depends not only on chemical signals but also on the physical structure of the environment surrounding cells. The extracellular matrix (ECM), a network of fibrous proteins and signaling molecules, provides not just a scaffold but also a rich landscape of mechanical and topographical cues that regulate cell behavior.
Among these cues, nanoscale patterns—such as the alternating grooves and ridges formed by collagen fibrils—play a critical role in guiding how stem cells adhere, spread, and differentiate. These features are neither uniform nor static; they change with age, injury, and disease. Despite their importance, replicating this dynamic nanoscale architecture in artificial materials remains a major challenge.
Researchers have previously fabricated grooved surfaces at the macro-, micro-, and nanoscale to study how physical topography influences cells. Static nanoscale grooves have been shown to affect stem cell shape, polarity, and lineage commitment. However, they cannot emulate the dynamic behavior of natural ECM, where structural features shift to regulate cell adhesion and signal transduction in real time.
Attempts to introduce switchable architectures have mostly operated at larger scales. Light-activated polymers and magnetically actuated systems have demonstrated dynamic behavior, but their resolution has been limited to micrometers. These approaches fail to reach the molecular dimensions at which integrin receptors—key components of the cell’s sensing machinery—interact with their ligands.
The absence of dynamic control at this critical tens-of-nanometers scale has limited our ability to study or influence stem cell behavior with precision.
In a study published in Advanced Materials (“Biomimetic Dynamics of Nanoscale Groove and Ridge Topography for Stem Cell Regulation”), a research team at Korea University presents a new material platform that addresses this limitation. The system enables reversible switching between nanoscale groove and ridge configurations in response to a magnetic field, operating at the scale relevant to integrin-mediated sensing.
This development offers a new route to dynamically control how stem cells interact with their environment, with direct implications for understanding mechanotransduction and improving regenerative material design.
Conceptual and magnetic characterization of the dynamic nanoscale system. (a) Schematic of groove and ridge switching via magnetic actuation of RGD-bearing nanoridges (MANs). Stem cell adhesion and differentiation are promoted when MANs protrude into the “ridge” state. (b) Magnetic properties of the MANs and nanogroove templates measured by vibrating sample magnetometry (VSM). (Image: Adapted from DOI:10.1002/adma.202419416. Panels 1a and 1b shown; panel 1c omitted for clarity. Reproduced under the terms of CC BY-NC-ND 4.0). (click on image to enlarge)
The researchers fabricated nanogroove templates with three groove widths—50, 80, and 110 nanometers—corresponding to dimensions relevant to integrin-presenting filopodia, which are thin membrane protrusions cells use to explore their surroundings. They attached magnetically responsive nanoridges, or MANs, to these grooves using flexible polymer linkers and coated them with RGD, a short peptide that facilitates cell adhesion through integrin binding. In the absence of a magnetic field, the RGD-bearing MANs remained buried within the grooves, limiting accessibility. When exposed to a magnetic field, the MANs rose above the groove surface, presenting the RGD signals and mimicking a ridge structure.
This transition was tunable and reversible. The magnetic lifting of the MANs converted the groove into a ridge, allowing for real-time control of ligand accessibility. The effectiveness of this system depended on groove width. In narrow 50-nanometer grooves, even the activated ridge state failed to provide enough space for effective filopodia engagement.
In wide 110-nanometer grooves, cells could access the RGD sites even when the MANs were buried, diminishing the impact of switching. The intermediate 80-nanometer grooves provided a balance: RGD sites were concealed in the groove state but became fully accessible when activated, producing a clear shift in cell response.
Human mesenchymal stem cells cultured on these surfaces showed distinct patterns of adhesion depending on groove width and switching state. On medium-width grooves, magnetic activation significantly increased integrin recruitment, focal adhesion formation, and spreading area. Cells also exhibited nuclear translocation of YAP and RUNX2, proteins associated with mechanical signaling and bone differentiation.
These effects were not observed in control samples lacking RGD, confirming that the response was driven by specific biochemical interactions rather than differences in surface shape alone.
To test whether the dynamic groove-to-ridge transitions could regulate stem cell behavior over time, the researchers applied a cyclic switching protocol. Magnetic activation was turned on and off every 24 hours, allowing for repeated changes between the two structural states. In medium-width grooves, this switching produced corresponding fluctuations in cell adhesion and mechanotransduction markers.
Cells in the final ridge state showed stronger integrin signaling and greater nuclear localization of YAP and RUNX2 than those left in the groove state. This indicated that cells were not only responding to static configurations but were sensitive to the timing and sequence of topographical cues.
The researchers further examined whether these dynamic interactions could influence long-term cell fate by assessing osteogenic differentiation. When cultured in differentiation-inducing conditions, stem cells on medium-width grooves that ended in the ridge state expressed significantly higher levels of RUNX2 and osteocalcin—markers of bone formation—than those ending in the groove state. The effect was abolished by inhibitors of cytoskeletal tension and mechanotransduction, confirming that the observed differentiation was mechanically mediated.
To explore potential biomedical applications, the system was tested in vivo. The team implanted the groove-ridge substrates under the skin of mice and introduced human stem cells directly onto them. Magnetic fields were applied externally to control the structural state of the substrate. After six hours, cells on magnetically activated (ridge state) substrates showed higher levels of adhesion and nuclear YAP and RUNX2, indicating successful mechanotransduction and early signs of differentiation.
Importantly, no local or systemic toxicity was observed, and the structural integrity of the materials remained intact throughout the experiment.
This work represents the first demonstration of dynamic groove-ridge switching at the molecular scale, precisely matched to the dimensions of filopodia and integrin ligands. By coupling magnetic responsiveness with nanoscale fabrication, the researchers created a surface that actively modulates biochemical accessibility in real time. This approach offers a new tool for investigating how cells interpret mechanical cues and provides a foundation for engineering biomaterials that guide stem cell behavior through controlled, dynamic topography.
The platform’s ability to operate at the molecular interface between cells and their environment could open new strategies in tissue regeneration, particularly in contexts where precise timing and location of stem cell activation are critical.
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