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

Abstract

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.

The upregulation of lamin A/C as a compensatory mechanism during tight junction disruption in renal tubular cells mediated by calcium oxalate crystals

“…With its multifaceted roles, lamin A/C requires many binding or interacting proteins to support its functions ( Malashicheva and Perepelina, 2021 ). For example, it interacts with cellular cytoskeletal complex, including F-actin, microtubule and intermediate filament, to maintain nuclear structure and function ( Antmen et al, 2021 , Chatzifrangkeskou et al, 2023 , Malashicheva and Perepelina, 2021 , Tariq et al, 2017 , Wang et al, 2023 ).…”

From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues

“…As can be seen by the enormous number of proteins involved and the extensive signaling crosstalk, it is evident that artificially modulating MT pathways can lead to unexpected results [13,280]. It is therefore of great importance to note that broader basic research is needed to elucidate cell-type specific and spatiotemporal aspects of MT, its exact regulation during the lifespan of an individual, and the dysregulation in pathological processes [281].…”

Nuclear Deformability of Breast Cells Analyzed from Patients with Malignant and Benign Breast Diseases

“…Previously, we showed that surfaces decorated with square prism pillars cause deformation of the cell body and nucleus and the extent of these alignments and deformations was malignancy specific. 24,25 Even though the responses of many cell lines toward these physical features were analyzed until now, a universally valid method for predicting cell response still lacks, especially in samples with a mixture of cells from different origins, co-cultures of cell lines, or cell populations. Patient-derived cells are mostly heterogeneous populations.…”

“…Although the molecular-based techniques are better detection methods than the traditional ones in terms of their specificity, they are unable to monitor the disease progression in its natural environment, expensive, and not easy to use. As an alternative, biomaterial-based detection systems have been developed recently. − They have the advantage of easy modulation of their surfaces and structures, which can create a microenvironment for the detection and culture of cancer cells.…”

“…In our earlier studies, we have developed novel biomaterial platforms with topographic features on their surfaces to successfully study the effect of physical surface cues on cellular processes like differentiation, carcinogenesis, EMT, and migration. − In our studies on the discrimination of breast cancer cells, breast cancer cell lines were used as model cells. Previously, we showed that surfaces decorated with square prism pillars cause deformation of the cell body and nucleus and the extent of these alignments and deformations was malignancy specific. , Even though the responses of many cell lines toward these physical features were analyzed until now, a universally valid method for predicting cell response still lacks, especially in samples with a mixture of cells from different origins, co-cultures of cell lines, or cell populations. Patient-derived cells are mostly heterogeneous populations.…”