Search

An improved understanding of the evolution of cell structure and viscoelasticity with cancer malignancy could enable the development of a new generation of biomarkers and methods for cancer diagnosis. Hence, in this study, we present the viscoelastic properties (moduli and viscosities) and the actin cytoskeletal structures of triple negative breast cancer (TNBC) cells with different metastatic potential. These include: MCF-10A normal breast cells (studied as a control); MDA-MB-468 cells (less metastatic TNBC cells), and MDA-MB-231 cells (highly metastatic TNBC cells). A combination of shear assay and digital imaging correlation (DIC) techniques is used to measure the local viscoelastic properties of live breast cells subjected to constant shear stress. The local moduli and viscosities of the nuclei and cytoplasm are characterized using a generalized Maxwell model, which is used to determine the time-dependent creep responses of cells. The nuclei are shown to be stiffer and more viscous than the cytoplasms of the normal breast cells and TNBC cells. The MCF-10A normal breast cells are found to be twice as stiff as the less metastatic MDA-MB-468 breast cancer cells and over ten times stiffer than the highly metastatic MDA-MB-231 breast cancer cells. Similar trends are also observed in the viscosities of the nuclei and the cytoplasms. The measured differences in cell viscoelastic properties are also associated with significant changes in the cell cytoskeletal structure, which is studied using confocal fluorescence microscopy. This reveals significant differences in the levels of actin expression and organization in TNBC cells as they become highly metastatic. Our results suggest that the shear assay measurements of cell viscoelastic properties may be used as effective biomarkers for TNBC diagnosis and screening. [ABSTRACT FROM AUTHOR]

Human mesenchymal stem cells (hMSCs) have shown promising potential in the field of regenerative medicine particularly in vascular tissue engineering. Optimal growing of MSCs into specific lineage requires a thorough understanding of the role of mechanobiology in MSC metabolism. Although effects of external physical cues (mechanical stimuli through external loading and scaffold properties) on regulation of MSC differentiation into Smooth muscle (SM) lineage have attracted widespread attention, fewer studies are available on mechanical characterization of single engineered MSCs which is vital in tissue development through proper mechanotransductive cell–environment interactions. In this study, we investigated effects of uniaxial tensile strain and transforming growth factor-β 1 (TGF-β 1 ) stimulations on mechanical properties of engineered MSCs and their F-actin cytoskeleton organization. Micropipette aspiration technique was used to measure mechanical properties of MSCs including mean Young׳s modulus ( E ) and the parameters of standard linear viscoelastic model. Compared to control samples, MSCs treated by uniaxial strain either with or without TGF-β 1 indicated significant increases in E value and considerable drop in creep compliance curve, while samples treated by TGF-β 1 alone met significant decreases in E value and considerable rise in creep compliance curve. Among treated samples, uniaxial tensile strain accompanied by TGF-β 1 stimulation not only caused higher stimulation in MSC differentiation towards SM phenotype at transcriptional level, but also created more structural integrity in MSCs due to formation of thick bundled F-actin fibers. Results can be applied in engineering of MSCs towards functional target cells and consequently tissue development. [ABSTRACT FROM AUTHOR]