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 migration in 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 motility in vitro, with the aim of mimicking elements of the environments in which cells move in 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 invasion in vivo. Finally, to compare across complex model systems, in vivo data, 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.
Highlights
| INTRODUCTIONIn order to best understand aspects of cellular motility, such as cell migration and cell invasion, we and others have developed sophisticated and controllable in vitro systems.[18,19,20,21,22,23] For example, synthetic biomaterials designed to mimic the extracellular matrix (ECM) allow us to conduct experiments to better understand cell movement in 3D including interactions between cells and their ECM
We describe the interrelation between these different motility measurements, the important differences in assays and reporting techniques used across the literature, and the potential predictive nature of in vitro assays to in vivo outcomes in a single model system
Given the rise of more physiological in vitro models that result in more complicated responses, this could be a first step to implement comparison of metrics across the field
Summary
In order to best understand aspects of cellular motility, such as cell migration and cell invasion, we and others have developed sophisticated and controllable in vitro systems.[18,19,20,21,22,23] For example, synthetic biomaterials designed to mimic the extracellular matrix (ECM) allow us to conduct experiments to better understand cell movement in 3D including interactions between cells and their ECM These in vitro systems, coupled with live microscopy, have allowed us to see cells move in response to extracellular signals and genetic manipulations that would be impossible in vivo. We describe the interrelation between these different motility measurements, the important differences in assays and reporting techniques used across the literature, and the potential predictive nature of in vitro assays to in vivo outcomes in a single model system
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