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Abstract Cell motility is a critical aspect of several processes, such as wound healing and immunity; however, it is dysregulated in cancer. Current limitations of imaging tools make it difficult to study cell migrationin vivo. To overcome this, and to identify drivers from the microenvironment that regulate cell migration, bioengineers have developed 2D (two‐dimensional) and 3D (three‐dimensional) tissue model systems in which to study cell motilityin vitro, with the aim of mimicking elements of the environments in which cells movein vivo. However, there has been no systematic study to explicitly relate and compare cell motility measurements between these geometries or systems. Here, we provide such analysis on our own data, as well as across data in existing literature to understand whether, and which, metrics are conserved across systems. To our surprise, only one metric of cell movement on 2D surfaces significantly and positively correlates with cell migration in 3D environments (percent migrating cells), and cell invasion in 3D has a weak, negative correlation with glioblastoma invasionin vivo. Finally, to compare across complex model systems,in vivodata, and data from different labs, we suggest that groups report an effect size, a statistical tool that is most translatable across experiments and labs, when conducting experiments that affect cellular motility.
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Confinement and substrate topography control cell migration in a 3D computational model
Abstract Cell movement in vivo is typically characterized by strong confinement and heterogeneous, three-dimensional environments. Such external constraints on cell motility are known to play important roles in many vital processes e.g. during development, differentiation, and the immune response, as well as in pathologies like cancer metastasis. Here we develop a physics-driven three-dimensional computational modeling framework that describes lamellipodium-based motion of cells in arbitrarily shaped and topographically structured surroundings. We use it to investigate the primary in vitro model scenarios currently studied experimentally: motion in vertical confinement, confinement in microchannels, as well as motion on fibers and on imposed modulations of surface topography. We find that confinement, substrate curvature and topography modulate the cell’s speed, shape and actin organization and can induce changes in the direction of motion along axes defined by the constraints. Our model serves as a benchmark to systematically explore lamellipodium-based motility and its interaction with the environment.
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- Award ID(s):
- 1707900
- PAR ID:
- 10154153
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Communications Physics
- Volume:
- 2
- Issue:
- 1
- ISSN:
- 2399-3650
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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