Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation

Abstract

In native microenvironment, diverse physical barriers exist to dynamically modulate stem cell recruitment and differentiation for tissue repair. In this study, nanoassembly‐based magnetic screens of various sizes are utilized, and they are elastically tethered over an RGD ligand (cell‐adhesive motif)‐presenting material surface to generate various nanogaps between the screens and the RGDs without modulating the RGD density. Large screens exhibiting low RGD distribution stimulate integrin clustering to facilitate focal adhesion, mechanotransduction, and differentiation of stem cells, which are not observed with small screens. Magnetic downward pulling of the large screens decreases the nanogaps, which dynamically suppress the focal adhesion, mechanotransduction, and differentiation of stem cells. Conversely, magnetic upward pulling of the small screens increases the nanogaps, which dynamically activates focal adhesion, mechanotransduction, and differentiation of stem cells. This regulation mechanism is also shown to be effective in the microenvironment in vivo. Further diversifying the geometries of the physical screens can further enable diverse modalities of multifaceted and safe unscreening of the distributed RGDs to unravel and modulate stem cell differentiation for tissue repair.

Integrating Soft Hydrogel with Nanostructures Reinforces Stem Cell Adhesion and Differentiation

“…In contrast, hMSCs without osteogenic medium showed significantly low levels of ALP and RUNX2 on MeHA hydrogel, indicating that undifferentiated hMSCs expressed very low basal expression levels of these two markers (Figure S6). These results are consistent with the previous findings that the activation of the mechanotransduction pathway (YAP) is positively associated with the osteogenic differentiation of stem cells [31,32]. More importantly, our findings illustrate that the implementation of the nanostructure re-arranges the spatial distribution of cell-adhesive peptides to reinforce stem cell adhesion and differentiation on soft matrix.…”

High-Content Screening and Analysis of Stem Cell-Derived Neural Interfaces Using a Combinatorial Nanotechnology and Machine Learning Approach

“…Nevertheless, it is still unclear how the diverse neural behaviors of NSCs of different origins and genetic backgrounds could be dedicatedly regulated by varying ECM-mediated biophysical cues [15]. Specifically, micro-/ nanotopographies of ECM, such as those present in protein fiber networks (i.e., collagen I/IV, fibronectin, and laminin), are abundant in many tissue types and known to profoundly affect adult neurogenesis through NSC cytoskeletal remodeling and modulation of biophysical signaling [16][17][18][19][20]. Researchers have thus made great efforts to understand the multifunctional roles of nanotopography on NSC fate decisions, encompassing the vast array of biophysical cues seen in natural ECM [21][22][23][24][25][26][27].…”

Magnetic supercluster particles for highly sensitive magnetic biosensing of proteins

“…However, their intrinsically small magnetic moment has limited the sensitive detection of target analytes, which in part prevents the widespread use of magnetic biosensors for medical diagnosis. It has been known that clustering SPIONs into a singleparticle form can increase the magnetic responsiveness of the nanoparticles as an aggregate [31], and the application of such particles as T 2 contrast enhancement agents in magnetic resonance imaging has also been demonstrated [32,33]. However, their utility in magnetic biosensors has not extensively been investigated so far, despite the assured advantage in signal transduction.…”