Mechanobiology of Collective Cell Migration in 3D Microenvironments

Abstract

Tumor cells invade individually or in groups, mediated by mechanical interactions between cells and their surrounding matrix. These multicellular dynamics are reminiscent of leader-follower coordination and epithelial-mesenchymal transitions (EMT) in tissue development, which may occur via dysregulation of associated molecular or physical mechanisms. However, it remains challenging to elucidate such phenotypic heterogeneity and plasticity without precision measurements of single cell behavior. The convergence of technological developments in live cell imaging, biophysical measurements, and 3D biomaterials are highly promising to reveal how tumor cells cooperate in aberrant microenvironments. Here, we highlight new results in collective migration from the perspective of cancer biology and bioengineering. First, we review the biology of collective cell migration. Next, we consider physics-inspired analyses based on order parameters and phase transitions. Further, we examine the interplay of metabolism and heterogeneity in collective migration. We then review the extracellular matrix, and new modalities for mechanical characterization of 3D biomaterials. We also explore epithelial-mesenchymal plasticity and implications for tumor progression. Finally, we speculate on future directions for integrating mechanobiology and cancer cell biology to elucidate collective migration.

MACC1-induced migration in tumors: Current state and perspective

“…Interestingly, the MACC1 stabilizing long non-coding RNA MACC1-AS is upregulated upon glucose deprivation, further promoting MACC1-induced glycolysis and antioxidant production under metabolic stress ( 220 ). Given the fact that the metabolic state and nutrient availability of cells have a large impact on cytoskeletal organization and migration ( 26 , 221 ), MACC1-induced metabolic adaptation might be another part of the MACC1-regulated migration in vivo .…”