Cell migration | EPFL Graph Search

Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations. Cells often migrate in response to specific external signals, including chemical signals and mechanical signals. Errors during this process have serious consequences, including intellectual disability, vascular disease, tumor formation and metastasis. An understanding of the mechanism by which cells migrate may lead to the development of novel therapeutic strategies for controlling, for example, invasive tumour cells. Due to the highly viscous environment (low Reynolds number), cells need to continuously produce forces in order to move. Cells achieve active movement by very different mechanisms. Many less complex prokaryotic organisms (and sperm cells) use flagella or cilia to propel themselves. Eukaryotic cell mi

3D multi-chamber fluidic systems for analysis of angiogenesis in biomaterials: development, characterization and applications

Carmen Bonvin

The cellular processes leading to capillary morphogenesis depend on external stimuli, in particular flow and morphogen gradients. Several devices have been designed to study these interactions in vitro. However, most of these devices allow a single experiment at a time, making it difficult to compare multiple conditions, which is needed for most biology experiments. Furthermore, it can be of great interest to use the same set of cells. Here we present two multi-chamber interstitial flow systems for side-by-side culture with the capability to follow the dynamics of individual cells. While a 9-chamber system was designed for cell culture or co-culture under radial flow, a multi-chamber migration assay allows studying cell migration into biomaterials under a constant flow profile. The effects of flow on lymphatic and blood endothelial cell morphology, as well as the extent of organization induced by VEGF, were observed. In addition, we demonstrated the feasibility of studying cell-cell interactions as well as cell-matrix interactions in a fibroblast and tumor cell co-culture. The two systems presented will allow for the study of interstitial flow and its effects

2009

Expression of E-Cadherin in Epithelial Cancer Cells Increases Cell Motility and Directionality through the Localization of ZO-1 during Collective Cell Migration

Hwanseok Jang

Collective cell migration of epithelial tumor cells is one of the important factors for elucidating cancer metastasis and developing novel drugs for cancer treatment. Especially, new roles of E-cadherin in cancer migration and metastasis, beyond the epithelial-mesenchymal transition, have recently been unveiled. Here, we quantitatively examined cell motility using micropatterned free edge migration model with E-cadherin re-expressing EC96 cells derived from adenocarcinoma gastric (AGS) cell line. EC96 cells showed increased migration features such as the expansion of cell islands and straightforward movement compared to AGS cells. The function of tight junction proteins known to E-cadherin expression were evaluated for cell migration by knockdown using sh-RNA. Cell migration and straight movement of EC96 cells were reduced by knockdown of ZO-1 and claudin-7, to a lesser degree. Analysis of the migratory activity of boundary cells and inner cells shows that EC96 cell migration was primarily conducted by boundary cells, similar to leader cells in collective migration. Immunofluorescence analysis showed that tight junctions (TJs) of EC96 cells might play important roles in intracellular communication among boundary cells. ZO-1 is localized to the base of protruding lamellipodia and cell contact sites at the rear of cells, indicating that ZO-1 might be important for the interaction between traction and tensile forces. Overall, dynamic regulation of E-cadherin expression and localization by interaction with ZO-1 protein is one of the targets for elucidating the mechanism of collective migration of cancer metastasis.

MDPI2021

Protrusion-retraction switches and traction forces in spontaneous cell polarization

Alicia Carine Bornert

Cell migration is a fundamental property of all animal cells which is involved in processes such as embryogenesis, immune response, tissue regeneration and cancer metastasis. Directional migration requires cell polarization which could happen in response to external signals but also spontaneously. Polarization involves the change in the cell edge activities from random distribution of protrusion and retraction to their separation into two large regions corresponding to the leading and trailing edges of the cell. Many studies investigated cytoskeletal mechanisms of protrusions and retractions but it is still not well understood how the cell orchestrates protrusion and retraction along its edge and what triggers transitions between these two types of activity. These questions are essential to understand both cell polarization and cycles of protrusion and retraction which characterize exploratory edge dynamics before polarization. This thesis focuses on the analysis of cell edge dynamics during the initiation of motion and on the mechanisms of transition (switches) between protrusion and retraction. We considered the cell polarization and protrusion-retraction cycles as two related phenomena and aimed to identify common mechanisms. Live cell imaging, cytoskeletal inhibitors, traction force microscopy, patterned substrates, micromanipulation, and computational analysis and modeling were used to examine cell polarization in the experimental model of fish epithelial keratocytes that are characterized by simple and regular shape and robust polarization and motion. We found that protrusion-retraction switches happened at maximal distance from the cell center both during cell edge fluctuation and directional motion and did not depend on the edge orientation with respect to the cell motion direction. Computational model demonstrated that switches at a threshold distance were sufficient for self-organization of edge activity leading to spontaneous polarization and stable cell shape and motion suggesting that distance-sensing is a fundamental mechanism of cell symmetry breaking. Next we investigated the mechanisms of distance-sensing focusing on two hypotheses: traction forces and tridimensional cell shape. Traction force may increase with the distance from the cell center (e.g., due to a build-up of actomyosin network) leading to detachment of the edge and initiation of retraction. We discovered that traction forces indeed increased with the distance and that protrusion-retraction switches occurred near maximal forces. Local external force also induced protrusion-retraction switch. However, inhibition of contractility reduced traction forces and abolished the dependence of force on the distance, but did not prevent cell polarization. Taken together, these results suggest that traction forces are sufficient, but not necessary mediators of distance-dependent switch and cell polarization. In an alternative mechanism, tridimensional shape of the cell edge may depend on the distance from the cell center and affect the balance of forces at the edge, inducing switches. We have locally modified this tridimensional force balance by using substrates with topographic features and showed that switches preferentially happen near these features. These results provide a novel framework to understand cell edge dynamics and symmetry breaking in terms of protrusion-retraction switches and physical force balance at the cell edge.

EPFL2016