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Micropatterned Surfaces Expose the Coupling between Actin Cytoskeleton‐Lamin/Nesprin and Nuclear Deformability of Breast Cancer Cells with Different Malignancies
Author(s) -
Antmen Ezgi,
Demirci Utkan,
Hasirci Vasif
Publication year - 2021
Publication title -
advanced biology
Language(s) - English
Resource type - Journals
ISSN - 2701-0198
DOI - 10.1002/adbi.202000048
Subject(s) - lamin , mechanotransduction , cytoskeleton , cytochalasin d , cancer cell , microbiology and biotechnology , actin , mechanobiology , chemistry , nuclear lamina , intermediate filament , cancer , biophysics , biology , cell , biochemistry , nuclear protein , nucleus , genetics , gene , transcription factor
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.