Nanotopography as Artificial Microenvironment for Accurate Visualization of Metastasis Development via Simulation of ECM Dynamics

Abstract

Metastatic progression is mediated by complex interactions between deregulated extracellular matrix (ECM) and cancer cells and remains a major challenge in cancer management. To investigate the role of ECM dynamics in promoting metastasis development, we developed an artificial microenvironment (AME) platform comprised of nanodot arrays of increasing diameter. Cells cultured on the platform showed increasing signs of mesenchymallike cell transition as AME diameter increased, suggesting accurate simulation of ECM-mediated gene regulation. Gene expression was analyzed to determine genes significant to transition, which were then used to select appropriate small molecule drugs for time course treatments. Our results suggest that the platform can identify critical target genes as well as possible drug candidates. Overall, the AME platform allows for the study of intricate ECM-induced gene expression trends across metastasis development that would otherwise be difficult to visualize in vivo and may open new avenues toward successful personalized cancer management.

Harnessing Focal Adhesions to Accelerate p53 Accumulation and Anoikis of A549 Cells Using Colloidal Self-Assembled Patterns (cSAPs)

“…The effect of surface topography on cancer cells facilitates the understanding of the tumor–ECM interactions and drug sensitivity . For instance, topographical features on poly­(ε-caprolactone) (PCL) upregulate focal adhesions indicated by prompted FAK and β1-integrin expressions in A549 cells .…”

“…Cell spreading area of A549 cells was reduced and more filopodia were observed on SiNW, which led to a decrease in cell migration. Other topographies, such as nanodots, nanopillars, nano/microwells, and nano/microgratings, have also been used to control the attachment of cancer cells. However, these studies only explore the particular interaction between cancer cells and one type of structure and did not investigate intracellular signaling.…”

Material Engineering in Gut Microbiome and Human Health

“…Additionally, biomaterials that amplify biochemical and/or biophysical signaling have also been applied to guide iPSC reprogramming and ESC pluripotency maintenance [ 117 ]. The effects of surface ligands, ligand densities, stiffness, and nanotopographies of ECM on stem cells and iPSC reprogramming are widely recognized [ 118 ]. For example, when substrates are modified with vitronectin-derived heparin-binding peptides, fibroblast adhesion to substrates is enhanced, leading to better proliferation and maintenance of the pluripotency of iPSCs during prolonged culture and passaging [ 119 ].…”

Near-Infrared Light-Activatable DNA Tentacles for Efficient Inhibition of Tumor Metastasis by Bio-Orthogonal Cell Assembly

“…8,9 A threedimensional porous network surrounds tumor cells in the interstitial matrix, facilitating cell communication and control-ling cell migration and differentiation. 10,11 The remodeling of the tumor's interstitial matrix induces a broad range of physiological changes that, in turn, affect numerous signal pathways, cell adhesion, migration, and tumor progression. 12,13 These changes facilitate the invasion of tumor cells through the stroma and their migration to nearby vessels, the first step of the metastatic cascade.…”