The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems

The epithelial-mesenchymal transition (EMT) is intrinsically linked to alterations of the intracellular cytoskeleton and the extracellular matrix. After EMT, cells acquire an elongated morphology with front/back polarity, which can be attributed to actin-driven protrusion formation as well as the gain of vimentin expression. Consequently, cells can deform and remodel the surrounding matrix in order to facilitate local invasion. In this review, we highlight recent bioengineering approaches to elucidate EMT and functional changes in the cytoskeleton. First, we review transitions between multicellular clusters and dispersed individuals on planar surfaces, which often exhibit coordinated behaviors driven by leader cells and EMT. Second, we consider the functional role of vimentin, which can be probed at subcellular length scales and within confined spaces. Third, we discuss the role of topographical patterning and EMT via a contact guidance like mechanism. Finally, we address how multicellular clusters disorganize and disseminate in 3D matrix. These new technologies enable controlled physical microenvironments and higher-resolution spatiotemporal measurements of EMT at the single cell level. In closing, we consider future directions for the field and outstanding questions regarding EMT and the cytoskeleton for human cancer progression.

Automated summary

The process of epithelial-mesenchymal transition (EMT) is intricately linked to alterations in the intracellular cytoskeleton and the extracellular matrix, leading to cellular elongation and polarity changes. Recent bioengineering approaches have shed light on the mechanisms behind EMT and cytoskeletal dynamics, with a focus on multicellular behavior, vimentin function, and contact guidance patterning. These technologies allow for a deeper understanding of EMT at the single cell level and offer insights into its implications for cancer progression.