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Fink, A.

Publications and source records attributed to Fink, A..

2 recordsLinked to original sources

Area and Geometry Dependence of Cell Migration in Asymmetric Two-State Micropatterns

Micro-structured surfaces provide a unique framework to probe cell migration and cytoskeletal dynamics in a standardized manner. Here, we report on the steady-state occupancy probability of cells in asymmetric two-state microstructures that consist of two fibronectin-coated adhesion sites connected by a thin guidance cue. In these dumbbell-like structures, cells transition between the two sites in a repeated and stochastic manner and average dwell times in the respective microenvironments are determined from the cell trajectories. We study the dynamics of human breast carcinoma cells (MDA-MB-231) in these microstructures as a function of area, shape and orientation of the adhesion sites. On square adhesive sites with different areas, we find that the occupancy probability ratio is directly proportional to the ratio of corresponding adhesion site areas. Sites of equal area but different shape lead to equal occupancy, if shapes are isotropic, e.g. squared or circular. In contrast, an asymmetry in the occupancy is induced by anisotropic shapes like rhombi, triangles or rectangles that enable motion in the direction perpendicular to the transition axis. Analysis of the 2D motion of cells between two rectangles with orthogonal orientation suggests that cellular transition rates depend on the cell polarisation induced by anisotropic micropatterns. Taken together, our results illustrate how two-state-micropatterns provide a dynamic migration assay with distinct dwell times and relative cell occupancy as readouts, which may potentially be useful to probe cell-microenvironment interactions.

biophysics

Disentangling the Behavioural Variability of Confined Cell Migration

Cell-to-cell variability is inherent to numerous biological processes, including cell migration. Quantifying and characterizing the variability of migrating cells is challenging, as it requires monitoring many cells for long time windows under identical conditions. Here, we observe the migration of single human breast cancer cells (MDA-MB-231) in confining two-state micropatterns. To describe the stochastic dynamics of this confined migration, we employ a dynamical systems approach. We identify statistics to measure the behavioural variance of the migration, which significantly exceed those predicted by a population-averaged stochastic model. This additional variance can be explained by the combination of an aging process and population heterogeneity. To quantify population heterogeneity, we decompose the cells into subpopulations of slow and fast cells, revealing the presence of distinct classes of dynamical systems describing the migration, ranging from bistable to limit cycle behaviour. Our findings highlight the breadth of migration behaviours present in cell populations.

biophysics