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Durotaxis and negative durotaxis: where should cells go?

ABSTRACT: Durotaxis and negative durotaxis are processes in which cell migration is directed by extracellular stiffness. Durotaxis is the tendency of cells to migrate toward stiffer areas, while negative durotaxis occurs when cells migrate toward regions with lower stiffness. The mechanisms of both processes are not yet fully understood. Additionally, the connection between durotaxis and negative durotaxis remains unclear. In this review, we compare the mechanisms underlying durotaxis and negative durotaxis, summarize the basic principles of both, discuss the possible reasons why some cell types exhibit durotaxis while others exhibit negative durotaxis, propose mechanisms of switching between these processes, and emphasize the challenges in the investigation of durotaxis and negative durotaxis.

SUBMITTER: Ji C

PROVIDER: S-EPMC10654570 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Durotaxis and negative durotaxis: where should cells go?

Ji Congcong C Huang Yuxing Y

Communications biology 20231116 1

Durotaxis and negative durotaxis are processes in which cell migration is directed by extracellular stiffness. Durotaxis is the tendency of cells to migrate toward stiffer areas, while negative durotaxis occurs when cells migrate toward regions with lower stiffness. The mechanisms of both processes are not yet fully understood. Additionally, the connection between durotaxis and negative durotaxis remains unclear. In this review, we compare the mechanisms underlying durotaxis and negative durotax ...[more]

PMID: 37973823

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Project description:Durotaxis is a type of directed cell migration in which cells respond to a gradient of extracellular stiffness. Using automated tracking of positional data for large sample sizes of single migrating cells, we investigated 1) whether cancer cells can undergo durotaxis; 2) whether cell durotactic efficiency varies depending on the regional compliance of stiffness gradients; 3) whether a specific cell migration parameter such as speed or time of migration correlates with durotaxis; and 4) whether Arp2/3, previously implicated in leading edge dynamics and migration, contributes to cancer cell durotaxis. Although durotaxis has been characterized primarily in nonmalignant mesenchymal cells, little is known about its role in cancer cell migration. Diffusible factors are known to affect cancer cell migration and metastasis. However, because many tumor microenvironments gradually stiffen, we hypothesized that durotaxis might also govern migration of cancer cells. We evaluated the durotactic potential of multiple cancer cell lines by employing substrate stiffness gradients mirroring the physiological stiffness encountered by cells in a variety of tissues. Automated cell tracking permitted rapid acquisition of positional data and robust statistical analyses for migrating cells. These durotaxis assays demonstrated that all cancer cell lines tested (two glioblastoma, metastatic breast cancer, and fibrosarcoma) migrated directionally in response to changes in extracellular stiffness. Unexpectedly, all cancer cell lines tested, as well as noninvasive human fibroblasts, displayed the strongest durotactic migratory response when migrating on the softest regions of stiffness gradients (2-7 kPa), with decreased responsiveness on stiff regions of gradients. Focusing on glioblastoma cells, durotactic forward migration index and displacement rates were relatively stable over time. Correlation analyses showed the expected correlation with displacement along the gradient but much less with persistence and none with cell speed. Finally, we found that inhibition of Arp2/3, an actin-nucleating protein necessary for lamellipodial protrusion, impaired durotactic migration.

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Durotaxis and negative durotaxis: where should cells go?

Publications

Durotaxis and negative durotaxis: where should cells go?

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