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Micropatterned Surfaces Expose the Coupling between Actin Cytoskeleton‐Lamin/Nesprin and Nuclear Deformability of Breast Cancer Cells with Different Malignancies.

Mechanotransduction proteins transfer mechanical stimuli through nucleo‐cytoskeletal coupling and affect the nuclear morphology of cancer cells. However, the contribution of actin filament integrity has never been studied directly. It is hypothesized that differences in nuclear deformability of cancer cells are influenced by the integrity of actin filaments. In this study, transparent micropatterned surfaces as simple tools to screen cytoskeletal and nuclear distortions are presented. Surfaces decorated with micropillars are used to culture and image breast cancer cells and quantify their deformation using shape descriptors (circularity, area, perimeter). Using two drugs (cytochalasin D and jasplakinolide), actin filaments are disrupted. Deformation of cells on micropillars is decreased upon drug treatment as shown by increased circularity. However, the effect is much smaller on benign MCF10A than on malignant MCF7 and MDAMB231 cells. On micropatterned surfaces, molecular analysis shows that Lamin A/C and Nesprin‐2 expressions decreased but, after drug treatment, increased in malignant cells but not in benign cells. These findings suggest that Lamin A/C, Nesprin‐2 and actin filaments are critical in mechanotransduction of cancer cells. Consequently, transparent micropatterned surfaces can be used as image analysis platforms to provide robust, high throughput measurements of nuclear deformability of cancer cells, including the effect of cytoskeletal elements.1

Summary of the nuclear deformability of cells on micropatterned surfaces and the action mechanism of the drugs inhibiting actins. A) SEM of patterned and smooth PMMA surfaces; B) Circularity value of three breast cancer cell lines (The distribution of shape descriptor values was non-normal and statistical analysis was carried out by Kruskal–Wallis nonparametric test, n≥  cells/surface, p< ., *p< ., **p< ., ***p< ., and ****p< .. n.s: not significant); C) Acting mechanism of actin inhibitory drugs: CytoD and Jasp.
Summary of the nuclear deformability of cells on micropatterned surfaces