Nanostructured Architectures Promote the Mesenchymal–Epithelial Transition for Invasive Cells

Abstract

Dynamic modulation of cellular phenotypes between the epithelial and mesenchymal statesthe epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET)plays an important role in cancer progression. Nanoscale topography of culture substrates is known to affect the migration and EMT of cancer cells. However, existing platforms heavily rely on simple geometries such as grooved lines or cylindrical post arrays, which may oversimplify the complex interaction between cells and nanotopography in vivo. Here, we use electrodeposition to construct finely controlled surfaces with biomimetic fractal nanostructures as a means of examining the roles of nanotopography during the EMT/MET process. We found that nanostructures in the size range of 100 to 500 nm significantly promote MET for invasive breast and prostate cancer cells. The “METed” cells acquired distinct expression of epithelial and mesenchymal markers, displayed perturbed morphologies, and exhibited diminished migration and invasion, even after the removal of a nanotopographical stimulus. The phosphorylation of GSK-3 was decreased, which further tuned the expression of Snail and modulated the EMT/MET process. Our findings suggest that invasive cancer cells respond to the geometries and dimensions of complex nanostructured architectures.

The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems

“…Indeed, the activity of these molecular regulators follows the observed gradient in YAP activity and EMT phenotype. Wang et al [114] patterned hierarchical textures in gold using electrochemical deposition techniques, inspired by the fractal-like topography of bone tissue (Fig. 6f, h).…”

Nanoscale Topographies for Corneal Endothelial Regeneration

“…The addition of instructive topographies on cell culture scaffolds could, therefore, provide significant advantages compared to conventional flat (smooth) 2D substrates, as the first can offer biophysical cues that more closely replicate those present in the native ECM. Surface topographies have already been shown to modulate mesenchymal-to-endothelial/epithelial transition [23][24][25][26] and vice versa [27][28][29][30] in several others applications. However, research focusing on the interaction between hCECs and surface topography of the culture substrate remains relatively less explored compared to other (corneal) cell types, despite the fact that growing evidence (as reported in the next sections as well as from preliminary work by our group) is showing that subcellular topographies can also have a significant impact on hCECs' expansion and differentiation.…”

Association between Cell Microenvironment Altered by Gold Nanowire Array and Regulation of Partial Epithelial‐Mesenchymal Transition

“…Recently, many researchers have studied the response of cells to mechanical forces on cells in terms of cell mechanobiology. [ 17–19 ] Various mechanical interactions between biological interfaces and nanostructures have been examined and utilized for biomedical applications. [ 20 ] Mechanically stimulating materials can modulate the physiological and pathological behavior of living tissues through cytomechanical transformation by transmitting mechanical signals, including stiffness, viscoelasticity, geometric constraints, and mechanical loads.…”

“…[ 7 ] In particular, several studies have attempted to explore the physical and physiological characteristics of cancer cells, including metastasis and epithelial‐mesenchymal transition (EMT) characteristics, by implementing microenvironmental changes using biomaterials and nanostructures. [ 19,22 ] Recent studies have confirmed that nanostructures can directly induce or reverse EMT phenotypes or can be used to deliver therapeutic molecules that modulate EMT‐related pathways. [ 19,23,24 ] EMT, one of the critical steps enabling cancer invasion and metastasis, is a group of complex cellular and biological processes that are common and distinct between cell and tissue types.…”

“…[ 19,22 ] Recent studies have confirmed that nanostructures can directly induce or reverse EMT phenotypes or can be used to deliver therapeutic molecules that modulate EMT‐related pathways. [ 19,23,24 ] EMT, one of the critical steps enabling cancer invasion and metastasis, is a group of complex cellular and biological processes that are common and distinct between cell and tissue types. [ 25 ] In general, as EMT processes, epithelial cells gradually lose their polarity and cell‐to‐cell junctions and downregulate the expression of epithelial biomarkers such as E‐cadherin and the epithelial cell adhesion molecule.…”