Geometrical constraints and physical crowding direct collective migration of fibroblasts

Abstract

Migrating cells constantly interact with their immediate microenvironment and neighbors. Although studies on single cell migration offer us insights into the molecular and biochemical signaling pathways, they cannot predict the influence of cell crowding and geometrical cues. Using microfabrication techniques, we examine the influence of cell density and geometrical constraints on migrating fibroblasts. Fibroblasts were allowed to migrate on fibronectin strips of different widths. Under such conditions, cells experience various physical guidance cues including boundary effect, confinement and contact inhibition from neighboring cells. Fibroblasts migrating along the edge of the fibronectin pattern exhibit spindle-like morphology, reminiscent of migrating cells within confined space and high cell density are associated with increased alignment and higher speed in migrating fibroblasts.

Direct but not indirect co-culture with osteogenically differentiated human bone marrow stromal cells increases RANKL/OPG ratio in human breast cancer cells generating bone metastases

“…Cluster number normalized to total cell number was indeed significantly higher in BOKL co-culture BMSCs, as compared to other conditions (p < 0.001, Figure 2 E). We observed a preferential direction of cell migration in direct co-culture as compared to culture with CM or GM (p < 0.01, Figure 2 F), probably due to cell contact guidance [ 18 ] and not to specific characteristics of cells that composed the monolayer, being this effect evident also in co-culture with MRC-5. Figure 2 G reports the quantification of BOKL proliferation in the different conditions, showing no significant differences between BOKL co-culture BMSCs and BOKL CM BMSCs.…”

Mechanical confinement triggers glioma linear migration dependent on formin FHOD3

“…This observation is extremely relevant to the glioma situation, since glioma cells proliferate along blood vessels, creating an extremely dense environment. Using micropatterns, Leong et al. (2013 ) found that fibroblasts migrating on the sides of large lines adopt a spindle shape and migrate in a similar manner as on thin lines and suggested that an increase in cell density promotes cell migration.…”

Engineered Models of Confined Cell Migration

“…Uniaxial migration was lost if the ECM line width exceeded 5 μm, and migration speed decreased (65). On very wide lines, the speed of fibroblasts migrating collectively decreased as the cells’ distance from the edge of the line increased (69). …”