Cytoskeletal role in differential adhesion patterns of normal fibroblasts and breast cancer cells inside silicon microenvironments

Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA.
Biomedical Microdevices (Impact Factor: 2.88). 12/2008; 11(3):585-95. DOI: 10.1007/s10544-008-9268-2
Source: PubMed


In this paper we studied differential adhesion of normal human fibroblast cells and human breast cancer cells to three dimensional (3-D) isotropic silicon microstructures and investigated whether cell cytoskeleton in healthy and diseased state results in differential adhesion. The 3-D silicon microstructures were formed by a single-mask single-isotropic-etch process. The interaction of these two cell lines with the presented microstructures was studied under static cell culture conditions. The results show that there is not a significant elongation of both cell types attached inside etched microstructures compared to flat surfaces. With respect to adhesion, the cancer cells adopt the curved shape of 3-D microenvironments while fibroblasts stretch to avoid the curved sidewalls. Treatment of fibroblast cells with cytochalasin D changed their adhesion, spreading and morphology and caused them act similar to cancer cells inside the 3-D microstructures. Statistical analysis confirmed that there is a significant alteration (P < 0.001) in fibroblast cell morphology and adhesion property after adding cytochalasin D. Adding cytochalasin D to cancer cells made these cells more rounded while there was not a significant alteration in their adhesion properties. The distinct geometry-dependent cell-surface interactions of fibroblasts and breast cancer cells are attributed to their different cytoskeletal structure; fibroblasts have an organized cytoskeletal structure and less deformable while cancer cells deform easily due to their impaired cytoskeleton. These 3-D silicon microstructures can be used as a tool to investigate cellular activities in a 3-D architecture and compare cytoskeletal properties of various cell lines.

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    • "The study of cell biomechanics has made great strides in the past decades as a result of advances in nanotechnologies enabling the manipulation and mechanical loading of single cells, and has brought significant new insight to how induced cell deformation and cyto-architecture remodeling impacts many aspects of human health and disease. The cytoskeleton provides mechanical support and integrity to the cell [19] but also plays a pivotal role in transducing mechanical stimuli from the microenvironment to intracellular signaling events that affect changes in gene expression, differentiation, adhesion [34], contractility, morphology and migration [49]. These are mechanically-oriented processes that are of critical importance in developmental biology, tissue homeostasis, tissue regeneration and wound healing [12], as well as cancer dissemination and metastasis [21]. "
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    • "Cells interact with different groups of macromolecules in the surrounding microenvironment that form the extracellular matrix (ECM). The ECM regulates cells' advancement, organisation, function and signals from adjacent cells (Nikkhah et al., 2009, Schindler et al., 2005). Cancer occurs when a normal cell fails to function properly, leading to abnormal cell growth that subsequently interrupts the organisation of tissue (Kaul- Ghanekar et al., 2009). "
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