The study demonstrates that amoeboid cells, which lack stable focal adhesions, can undergo durotaxis - directional migration along substrate stiffness gradients. Using an imaging-based cell migration device with stiffness gradients, the authors observed that T cells, neutrophils, and the amoeboid protist Dictyostelium all exhibited durotactic behavior, preferentially migrating towards stiffer regions of the substrate.
The underlying mechanism was found to involve the polarized localization of non-muscle myosin IIA (NMIIA) towards the softer end of the stiffness gradient, rather than differential actin flow as seen in mesenchymal cell durotaxis. Inhibition of NMIIA activity abolished the durotactic behavior, while enhancing myosin contractility increased durotaxis.
Computational modeling of the amoeboid cell as an active gel droplet captured the experimental observations, suggesting that the diffusion rate of NMIIA, which is sensitive to substrate stiffness, drives its polarized distribution and enables durotaxis. The authors further demonstrated that the initial local stiffness sensed by the cell can modulate the durotactic response, with cells on softer regions of the gradient exhibiting stronger durotaxis.
These findings reveal that amoeboid cells, despite their lack of stable adhesions, can sense and respond to mechanical cues in their microenvironment, which may have important implications for immune cell migration, wound healing, and cancer metastasis.
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by Yi,X., Chen,... um www.biorxiv.org 04-13-2023
https://www.biorxiv.org/content/10.1101/2023.04.13.536664v2Tiefere Fragen