Directed cell migration is essential for cells to efficiently migrate in physiological and pathological processes. While migrating in their native environment, cells interact with multiple types of cues, such as mechanical and chemical signals. The role of chemical guidance via chemotaxis has been studied in the past, the understanding of mechanical guidance of cell migration via durotaxis remained unclear until very recently. Nonetheless, durotaxis has become a topic of intensive research and several advances have been made in the study of mechanically guided cell migration across multiple fields. Thus, in this article we provide a state of the art about durotaxis by discussing in silico, in vitro and in vivo data. We also present insights on the general mechanisms by which cells sense, transduce and respond to environmental mechanics, to then contextualize these mechanisms in the process of durotaxis and explain how cells bias their migration in anisotropic substrates. Furthermore, we discuss what is known about durotaxis in vivo and we comment on how haptotaxis could arise from integrating durotaxis and chemotaxis in native environments.

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Embryogenesis, tissue repair and cancer metastasis rely on collective cell migration. In vitro studies propose that cells are stiffer while migrating in stiff substrates, but softer when plated in compliant surfaces which are typically considered as non-permissive for migration. Here we show that cells within clusters from embryonic tissue dynamically decrease their stiffness in response to the temporal stiffening of their native substrate to initiate collective cell migration. Molecular and mechanical perturbations of embryonic tissues reveal that this unexpected mechanical response involves a mechanosensitive pathway relying on Piezo1-mediated microtubule deacetylation. We further show that decreasing microtubule acetylation and consequently cluster stiffness is sufficient to trigger collective cell migration in soft non-permissive substrates. This suggests that reaching an optimal cluster-to-substrate stiffness ratio is essential to trigger the onset of this collective process. Overall, these in vivo findings challenge the current understanding of collective cell migration and its physiological and pathological roles.

The transcription factor Hif-1α regulates epithelial to mesenchymal transition and neural crest cell chemotaxis in Xenopus. Hif-1α is only stabilised under low oxygen levels, and the in vivo stabilisation of this factor in neural crest cells is poorly understood. Multiple oxygen-independent Hif-1α regulators have been described in cell cultures and cancer models. Among these, the PDGF pathway has been linked to neural crest development. The present study established a connection between the Pdgf pathway and Hif-1α stabilisation in zebrafish. Specifically, embryos with a disrupted Pdgf pathway were rescued by employing hif-1α mRNA through qPCR and immunohistochemistry techniques. The data suggest that oxygen levels in the neural crest are normal and that Pdgf1aa regulates neural crest migration through Hif-1α expression.

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