REGULATION OF SHAPE DYNAMICS AND ACTIN POLYMERIZATION DURING COLLECTIVE CELL MIGRATION

This thesis aims to understand how cells coordinate their motion during collective migration. As previously shown, the motion of individually migrating cells is governed by wave-like cell shape dynamics. The mechanisms that regulate these dynamic behaviors in response to extracellular environment remain largely unclear. I applied shape dynamics analysis to Dictyostelium cells migrating in pairs and in multicellular streams and found that wave-like membrane protrusions are highly coupled between touching cells. I further characterized cell motion by using principle component analysis (PCA) to decompose complex cell shape changes into a serial shape change modes, from which I found that streaming cells exhibit localized anterior protrusion, termed front narrowing, to facilitate cell-cell coupling. I next explored cytoskeleton-based mechanisms of cell-cell coupling by measuring the dynamics of actin polymerization. Actin polymerization waves observed in individual cells were significantly suppressed in multicellular streams. Streaming cells exclusively produced F-actin at cell-cell contact regions, especially at cell fronts. I demonstrated that such restricted actin polymerization is associated with cell-cell coupling, as reducing actin polymerization with Latrunculin A leads to the assembly of F-actin at the side of streams, the decrease of front narrowing, and the decoupling of protrusion waves. My studies also suggest that collective migration is guided by cell-surface interactions. I examined the aggregation of Dictyostelim cells under distinct conditions and found that both chemical compositions of surfaces and surface-adhesion defects in cells result in altered collective migration patterns. I also investigated the shape dynamics of cells suspended on PEG-coated surfaces, which showed that coupling of protrusion waves disappears on touching suspended cells. These observations indicate that collective migration requires a balance between cell-cell and cell-surface adhesions. I hypothesized such a balance is reached via the regulation of cytoskeleton. Indeed, I found cells actively regulate cytoskeleton to retain optimal cell-surface adhesions on varying surfaces, and cells lacking the link between actin and surfaces (talin A) could not retain the optimal adhesions. On the other hand, suspended cells exhibited enhanced actin filament assembly on the periphery of cell groups instead of in cell-cell contact regions, which facilitates their aggregation in a clumping fashion.

ESSAYS ON DISPLACED WORKERS AND RESIDENTIAL MIGRATION

In this dissertation, I explore how workers’ human capital, local industry composition, and business cycles affect employment outcomes and residential migration for job losers and other workers. I first examine whether the poor employment outcomes of job losers are due to a lack of jobs that require their human capital within their local labor market. I answer this question by analyzing the extent to which the industry composition in the job loser’s local labor market affects employment outcomes when job loss occurs during expansions and during recessions. I find that if job losers reside in an area with a high employment concentration of their original industry of employment, they are 2.1-2.8 percent more likely to be re-employed at another job if job loss occurs during an expansion; I find an insignificant relationship in most specifications when job loss occurs during a recession, and in some specifications I even find a negative relationship between industry concentration and employment. I conclude that the industry composition within an area matters for job losers, since firms are more willing to hire workers from within their own industry, as these workers have more relevant accumulated human capital. However, firms are less likely to hire during a recession, making job losers’ human capital less important for job finding. Next, Erika McEntarfer, Henry Hyatt, and I examine whether the business cycle affects earnings changes for job losers, and the factors that explain these differences across time. We find that job losers who lost their job during the Great Recession have earnings changes that are 10 percent more negative relative to other job losers from other periods. This result is driven primarily by longer nonemployment lengths and worse subsequent job matches. Finally, Erika McEntarfer, Henry Hyatt, Alexandria Zhang, and I explore the extent to which residential migration is driven by job opportunities. We use four databases and find that changes in job moves explain some of the changes in residential migration, but the relationship is not as strong as previously documented. We find that migration patterns differ across databases, with some databases documenting steeper declines and more cyclicality.