Native extracellular matrix (ECM) can exhibit cyclic nanoscale stretching and shrinking of ligands to regulate complex cell–material interactions. Designing materials that allow cyclic control of changes in intrinsic ligand‐presenting nanostructures in situ can emulate ECM dynamicity to regulate cellular adhesion. Unprecedented remote control of rapid, cyclic, and mechanical stretching (“ON”) and shrinking (“OFF”) of cell‐adhesive RGD ligand‐presenting magnetic nanocoils on a material surface in five repeated cycles are reported, thereby independently increasing and decreasing ligand pitch in nanocoils, respectively, without modulating ligand‐presenting surface area per nanocoil. It is demonstrated that cyclic switching “ON” (ligand nanostretching) facilitates time‐regulated integrin ligation, focal adhesion, spreading, YAP/TAZ mechanosensing, and differentiation of viable stem cells, both in vitro and in vivo. Fluorescence resonance energy transfer (FRET) imaging reveals magnetic switching “ON” (stretching) and “OFF” (shrinking) of the nanocoils inside animals. Versatile tuning of physical dimensions and elements of nanocoils by regulating electrodeposition conditions is also demonstrated. The study sheds novel insight into designing materials with connected ligand nanostructures that exhibit nanocoil‐specific nano‐spaced declustering, which is ineffective in nanowires, to facilitate cell adhesion. This unprecedented, independent, remote, and cytocompatible control of ligand nanopitch is promising for regulating the mechanosensing‐mediated differentiation of stem cells in vivo.

Of various molecular diagnostic assays, the real-time reverse transcription polymerase chain reaction is considered the gold standard for infection diagnosis, despite critical drawbacks that limit rapid detection and accessibility. To confront these issues, several nanoparticle-based molecular detection methods have been developed to a great extent, but still possess several challenges. In this study, a novel nucleic acid amplification method termed nanoparticle-based surface localized amplification (nSLAM) is paired with electrochemical detection (ECD) to develop a nucleic acid biosensor platform that overcomes these limitations. The system uses primer-functionalized Fe 3 O 4 −Au core−shell nanoparticles for nucleic acid amplification, which promotes the production of amplicons that accumulate on the nanoparticle surfaces, inducing significantly amplified currents during ECD that identify the presence of target genetic material. The platform, applying to the COVID-19 model, demonstrates an exceptional sensitivity of ∼1 copy/μL for 35 cycles of amplification, enabling the reduction of amplification cycles to 4 cycles (∼7 min runtime) using 1 fM complementary DNA. The nSLAM acts as an accelerator that actively promotes and participates in the nucleic acid amplification process through direct polymerization and binding of amplicons on the nanoparticle surfaces. This ultrasensitive fast-response system is a promising method for detecting emerging pathogens like the coronavirus and can be extended to detect a wider variety of biomolecules.

Developing materials with the capability of changing their innate features can help to unravel direct interactions between cells and ligand‐displaying features. This study demonstrates the grafting of magnetic nanohelices displaying cell‐adhesive Arg‐Gly‐Asp (RGD) ligand partly to a material surface. These enable nanoscale control of rapid winding (“W”) and unwinding (“UW”) of their nongrafted portion, such as directional changes in nanohelix unwinding (lower, middle, and upper directions) by changing the position of a permanent magnet while keeping the ligand‐conjugated nanohelix surface area constant. The unwinding (“UW”) setting cytocompatibility facilitates direct integrin recruitment onto the ligand‐conjugated nanohelix to mediate the development of paxillin adhesion assemblies of macrophages that stimulate M2 polarization using glass and silicon substrates for in vitro and in vivo settings, respectively, at a single cell level. Real time and in vivo imaging are demonstrated that nanohelices exhibit reversible unwinding, winding, and unwinding settings, which modulate time‐resolved adhesion and polarization of macrophages. It is envisaged that this remote, reversible, and cytocompatible control can help to elucidate molecular‐level cell–material interactions that modulate regenerative/anti‐inflammatory immune responses to implants.

Cell microenvironment is an essential factor in determining cell growth and cell fate. Many studies have been carried out to understand the functions and mechanisms of small molecules or growth factors/cytokines; however, the effects of the physical environment on cells are relatively unknown. Changes in the cell's physical microenvironment affect cell adhesion and modify intracellular signaling controlled by adhesion properties, resulting in altering the cytoskeletal structure and cellular properties. Herein, it is demonstrated that the changes in cell adhesion can affect the epithelial‐mesenchymal transition (EMT) of epithelial cells by implementing a cell microenvironment with a gold (Au) nanowire array to influence cell adhesion. A forcible decrease in cell adhesion leads to the downregulation of epithelial biomarkers and the upregulation of mesenchymal biomarkers. The results of force‐distance experiments using atomic force microscopy showed that the overall stiffness of epithelial cells declined similarly to the case for mesenchymal‐like cells. With this comprehensive analysis of cellular properties, a physical microenvironment for cell adhesion alteration is suggested, that can induce mesenchymal characteristics in both epithelial and mesenchymal cells through partial EMT.

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Macrophage Polarization In article number 2103409, Young Keun Kim, Heemin Kang, and co‐workers present an adhesive nanohelical nanostructure that is partially affixed to the surface, which can be actively manipulated to wind in any direction. This active winding modulates integrin recruitment onto the adhesive nanostructure at a single cell level to mediate an assembly of adhesion structures that stimulates regenerative immunomodulation.