Mechanical observables of cancer invasion: actin, adhesion, and metastatic plasticity

Vollständiger Abstract

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Cancer invasion is commonly classified through epithelial-mesenchymal plasticity, yet cells with similar transcriptional states can differ substantially in force production, cytoskeletal organization and collective mobility. We critically examine whether mechanical measurements can supply information that is not already contained in molecular or histopathological classifications. The available evidence does not justify a universal five-dimensional phase space. It supports a more restrained hierarchy: primary measurements (filament orientation, cortical tension, substrate traction, cell and nuclear boundaries, and velocity fields), derived descriptors (polarity, field-specific normalized nematic order, shape and density metrics), and tissue-scale constructions (orientation fields, defects and inferred unjamming states). These levels are coupled and often mathematically dependent. We correct several common conflations. Traction-force microscopy recovers substrate traction through an inverse mechanical model; it does not directly measure intrinsic cortical active stress. Isotropic cortical contractility must be separated from anisotropic nematic stress. Structural actin order must likewise be distinguished from apolar alignment calculated from an optical-flow field; the latter is a dynamic image-derived descriptor, not a direct measurement of filament orientation or active stress. The vertex model threshold p 0 * ≃ 3.81 is a model parameter, not a universal cutoff for segmented tumor cells. Patient-tissue unjamming maps instead use multivariate shape-density information, including cell-and-nucleus shape (CeNuS) and nuclear number density. We evaluate evidence supporting and opposing the independence of unjamming from epithelial-mesenchymal transition, the context-dependent effects of contractility, and the proposed causal role of topological defects. Our conclusion is deliberately conditional: mechanical observables are most credible as complementary, scale-specific measurements whose incremental value must be established against EMT/EMP state, tumor grade and tissue architecture in the same specimens. This formulation retains the explanatory power of mechanics while making its assumptions, dependencies and clinical limits explicit.