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Here we demonstrate how cells to spontaneously ‘sense’ and follow extracellular matrix alignment through anisotropic cell–substratum forces. Further, this work demonstrates control of contact guidance by a balance of cell–substratum, and cell–cell interactions, modulated by cell phenotype-specific cytoskeletal arrangements.
This study demonstrated that the optimal mechanical stiffness of the substrate to which cells adhere, in terms of cell spreading and migration, can be shifted as predicted by the motor-clutch model, i.e. by coordinately changing the motor-clutch level. Thus, the principle difference between neurons and glioma cells is the motor-clutch level, with glioma exhibiting a much higher level of both, and therefore a much higher optimum. The study demonstrates the predictive power of the motor-clutch modeling, and shows how cells establish their optimum.
Minireview of mechanotransduction and modeling cell dynamics and the highlight of recent work interfacing the motor-clutch model framework to a mechanically evolving extracellular matrix.
This study demonstrated that the epithelial-to-mesenchymal transition (EMT) in breast epithelial cells is largely mediated by a coordinate increase in motors and clutches, with a somewhat larger increase in clutches relative to motors. The findings suggest new ways to inhibit EMT, which is a key step in invasion and metastasis.
This work demonstrates the unique dynamics of cancer stem cells during directed cell migration by contact guidance in aligned collagenous extracellular matrix. Further, we show that a high degree of phenotypic plasticity and increased protrusive activity emerge as vital facilitators of rapid contact guided migration of CSCs.
This study demonstrated that there is an optimal level of CD44 that correlates with fastest cell migration in an induced mouse model for glioblastoma. We found that at intermediate CD44 level cells migrated fastest and that mice die most rapidly. If the level of CD44 is either increased or decreased, then migration drops and survival is extended. When we examined published human transcript data, we found the same trend with respect to human high grade glioma survival, even though there was no linear correlation. Thus, our results illustrate the functional relationship between cell migration and survival, and more generally point toward biomarkers being treated as non-monotonic predictors such that survival depends biphasically upon expression level, i.e. there is an optimal level of gene expression leads to poorest outcomes.