Disentangling the behavioural variability of confined cell migration
Ontology highlight
ABSTRACT:
SUBMITTER: Bruckner D
PROVIDER: S-EPMC7061702 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Cell dispersion from a confined area is fundamental in a number of biological processes, including cancer metastasis. To date, a quantitative understanding of the interplay of single-cell motility, cell proliferation, and intercellular contacts remains elusive. In particular, the role of E- and N-cadherin junctions, central components of intercellular contacts, is still controversial. Combining theoretical modeling with in vitro observations, we investigate the collective spreading behavior of colonies of human cancer cells (T24). The spreading of these colonies is driven by stochastic single-cell migration with frequent transient cell-cell contacts. We find that inhibition of E- and N-cadherin junctions decreases colony spreading and average spreading velocities, without affecting the strength of correlations in spreading velocities of neighboring cells. Based on a biophysical simulation model for cell migration, we show that the behavioral changes upon disruption of these junctions can be explained by reduced repulsive excluded volume interactions between cells. This suggests that in cancer cell migration, cadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than cohesive interactions between cells, thereby promoting efficient cell spreading during collective migration.
| S-EPMC8758422 | biostudies-literature
Project description:The migratory dynamics of cells in physiological processes, ranging from wound healing to cancer metastasis, rely on contact-mediated cell-cell interactions. These interactions play a key role in shaping the stochastic trajectories of migrating cells. While data-driven physical formalisms for the stochastic migration dynamics of single cells have been developed, such a framework for the behavioral dynamics of interacting cells still remains elusive. Here, we monitor stochastic cell trajectories in a minimal experimental cell collider: a dumbbell-shaped micropattern on which pairs of cells perform repeated cellular collisions. We observe different characteristic behaviors, including cells reversing, following, and sliding past each other upon collision. Capitalizing on this large experimental dataset of coupled cell trajectories, we infer an interacting stochastic equation of motion that accurately predicts the observed interaction behaviors. Our approach reveals that interacting noncancerous MCF10A cells can be described by repulsion and friction interactions. In contrast, cancerous MDA-MB-231 cells exhibit attraction and antifriction interactions, promoting the predominant relative sliding behavior observed for these cells. Based on these experimentally inferred interactions, we show how this framework may generalize to provide a unifying theoretical description of the diverse cellular interaction behaviors of distinct cell types.
| S-EPMC7896326 | biostudies-literature
Project description:Cell migration is a critical process for diverse (patho)physiological phenomena. Intriguingly, cell migration through physically confined spaces can persist even when typical hallmarks of 2D planar migration, such as actin polymerization and myosin II-mediated contractility, are inhibited. Here, we present an integrated experimental and theoretical approach ("Osmotic Engine Model") and demonstrate that directed water permeation is a major mechanism of cell migration in confined microenvironments. Using microfluidic and imaging techniques along with mathematical modeling, we show that tumor cells confined in a narrow channel establish a polarized distribution of Na+/H+ pumps and aquaporins in the cell membrane, which creates a net inflow of water and ions at the cell leading edge and a net outflow of water and ions at the trailing edge, leading to net cell displacement. Collectively, this study presents an alternate mechanism of cell migration in confinement that depends on cell-volume regulation via water permeation.
| S-EPMC4365996 | biostudies-literature
Project description:Cellular processes are regulated by various mechanical and physical factors in their local microenvironment such as geometric confinements, cell-substrate interactions, and cell-cell contact. Systematic elucidation of these regulatory mechanisms is crucial for fundamental understanding of cell biology and for rational design of biomedical devices and regenerative medicine. Here, we report a generally applicable plasma lithography technique, which performs selective surface functionalization on large substrate areas, for achieving long-term, stable confinements with length scales from 100 nm to 1 cm toward the investigation of cell-microenvironment interactions. In particular, we applied plasma lithography for cellular confinement of neuroblastomas, myoblasts, endothelial cells, and mammary gland epithelial cells, and examined the motion of mouse embryonic fibroblasts in directionality-confined environments for studying the effect of confinements on migratory behavior. In conjunction with live cell imaging, the distance traveled, velocity, and angular motion of individual cells and collective cell migration behaviors were measured in confined environments with dimensions comparable to a cell. A critical length scale that a cell could conceivably occupy and migrate to was also identified by investigating the behaviors of cells using confined environments with subcellular length scales.
| S-EPMC3023939 | biostudies-literature
Project description:Anthropogenic macrolitter (>0.5 cm) in rivers is of increasing concern. It has been found to have an adverse effect on riverine ecosystem health, and the livelihoods of the communities depending on and living next to these ecosystems. Yet, little is known on how macrolitter reaches and propagates through these ecosystems. A better understanding of macrolitter transport dynamics is key in developing effective reduction, preventive, and cleanup measures. In this study, we analyzed a novel dataset of citizen science riverbank macrolitter observations in the Dutch Rhine-Meuse delta, spanning two years of observations on over 200 unique locations, with the litter categorized into 111 item categories according to the river-OSPAR protocol. With the use of regression models, we analyzed how much of the variation in the observations can be explained by hydrometeorology, observer bias, and location, and how much can instead be explained by temporal trends and seasonality. The results show that observation bias is very low, with only a few exceptions, in contrast with the total variance in the observations. Additionally, the models show that precipitation, wind speed, and river flow are all important explanatory variables in litter abundance variability. However, the total number of items that can significantly be explained by the regression models is 19% and only six item categories display an R2 above 0.4. This suggests that a very substantial part of the variability in macrolitter abundance is a product of chance, caused by unaccounted (and often fundamentally unknowable) stochastic processes, rather than being driven by the deterministic processes studied in our analyses. The implications of these findings are that for modeling macrolitter movement through rivers effectively, a probabilistic approach and a strong uncertainty analysis are fundamental. In turn, point observations of macrolitter need to be planned to capture short-term variability.
| S-EPMC8154362 | biostudies-literature
Project description:Though cell and nuclear deformability are expected to influence efficiency of confined migration, their individual and collective influence on migration efficiency remains incompletely understood. In addition to cell intrinsic properties, the relevance of cell extrinsic factors on confined migration, if any, has not been adequately explored. Here we address these questions using a statistical mechanics-based stochastic modeling approach where cell/nuclear dimensions and their deformability are explicitly taken into consideration. In addition to demonstrating the importance of cell softness in sustaining confined migration, our results suggest that dynamic tuning of cell and nuclear properties at different stages of migration is essential for maximizing migration efficiency. Our simulations also implicate confinement shape and confinement history as two important cell extrinsic regulators of cell invasiveness. Together, our findings illustrate the strength of a multicompartment model in dissecting the contributions of multiple factors that collectively influence confined cell migration.
| S-EPMC6080655 | biostudies-literature
Project description:Recent in vitro and in vivo studies have highlighted the importance of the cell nucleus in governing migration through confined environments. Microfluidic devices that mimic the narrow interstitial spaces of tissues have emerged as important tools to study cellular dynamics during confined migration, including the consequences of nuclear deformation and nuclear envelope rupture. However, while image acquisition can be automated on motorized microscopes, the analysis of the corresponding time-lapse sequences for nuclear transit through the pores and events such as nuclear envelope rupture currently requires manual analysis. In addition to being highly time-consuming, such manual analysis is susceptible to person-to-person variability. Studies that compare large numbers of cell types and conditions therefore require automated image analysis to achieve sufficiently high throughput. Here, we present an automated image analysis program to register microfluidic constrictions and perform image segmentation to detect individual cell nuclei. The MATLAB program tracks nuclear migration over time and records constriction-transit events, transit times, transit success rates, and nuclear envelope rupture. Such automation reduces the time required to analyze migration experiments from weeks to hours, and removes the variability that arises from different human analysts. Comparison with manual analysis confirmed that both constriction transit and nuclear envelope rupture were detected correctly and reliably, and the automated analysis results closely matched a manual analysis gold standard. Applying the program to specific biological examples, we demonstrate its ability to detect differences in nuclear transit time between cells with different levels of the nuclear envelope proteins lamin A/C, which govern nuclear deformability, and to detect an increase in nuclear envelope rupture duration in cells in which CHMP7, a protein involved in nuclear envelope repair, had been depleted. The program thus presents a versatile tool for the study of confined migration and its effect on the cell nucleus.
| S-EPMC5896979 | biostudies-literature
Project description:Cell migration is a pivotal step in metastatic process, which requires cancer cells to navigate a complex spatially-confined environment, including tracks within blood vessels and in the vasculature of target organs. Here it is shown that during spatially-confined migration, the expression of insulin-like growth factor-binding protein 1 (IGFBP1) is upregulated in tumor cells. Secreted IGFBP1 inhibits AKT1-mediated phosphorylation of mitochondrial superoxide dismutase (SOD2) serine (S) 27 and enhances SOD2 activity. Enhanced SOD2 attenuates mitochondrial reactive oxygen species (ROS) accumulation in confined cells, which supports tumor cell survival in blood vessels of lung tissues, thereby accelerating tumor metastasis in mice. The levels of blood IGFBP1 correlate with metastatic recurrence of lung cancer patients. This finding reveals a unique mechanism by which IGFBP1 sustains cell survival during confined migration by enhancing mitochondrial ROS detoxification, thereby promoting tumor metastasis.
| S-EPMC10375137 | biostudies-literature
Project description:We show that confined migration results in predominantly decreased chromatin accessibility, consistent with the increased heterochromatin marks staining. A small fraction of ATAC-seq peaks shows increased accessibility at gene promoters of diverse pathways, such as chromatin silencing, tumor invasion, and DNA damage response; whereas the majority shows decreased accessibility at intergenic regions near centromeres or telomeres, suggesting possible heterochromatin spreading.
2022-08-10 | GSE181247 | GEO
Project description:Cell migration is heavily interconnected with plasma membrane protrusion and retraction (collectively termed "membrane dynamics"). This makes it difficult to distinguish regulatory mechanisms that differentially influence migration and membrane dynamics. Yet such distinctions may be valuable given evidence that cancer cell invasion in 3D may be better predicted by 2D membrane dynamics than by 2D cell migration, implying a degree of functional independence between these processes. Here, we applied multi-scale single cell imaging and a systematic statistical approach to disentangle regulatory associations underlying either migration or membrane dynamics. This revealed preferential correlations between membrane dynamics and F-actin features, contrasting with an enrichment of links between cell migration and adhesion complex properties. These correlative linkages were often non-linear and therefore context-dependent, strengthening or weakening with spontaneous heterogeneity in cell behavior. More broadly, we observed that slow moving cells tend to increase in area, while fast moving cells tend to shrink, and that the size of dynamic membrane domains is independent of cell area. Overall, we define macromolecular features preferentially associated with either cell migration or membrane dynamics, enabling more specific interrogation and targeting of these processes in future.
| S-EPMC4527765 | biostudies-literature