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Cell traction forces (CTF) generated by the actomyosin cytoskeleton onto a substrate or extracellular matrix (ECM) are essential for many biological processes, including developmental morphogenesis, tissue homeostasis, and cancer metastasis. Because the cellular physical properties are closely related to the pathological states of the cells, affected by various physicochemical stimuli from their neighboring cells or surrounding environments, it is crucial to develop a quantitative measure for cellular responses to these external stimuli. Since the pioneering work of Harris et al. in 1980s1, traction force microscopy (TFM) has been widely used as a standard tool that allows the optical measurement of cellular tractions exerted on 2- and 3-dimensional soft elastic substrates. Recently, there have been many technical advances in conventional TFM to enhance its spatial and temporal resolutions as well as the range of applicability. In this review, we provide a survey on the recent advancement in TFM, especially with a special emphasis on platforms that can externally apply various stimuli such as fluid shear, mechanical tension or compression, biochemical factors, and electric field in a physiologically relevant regime. [ABSTRACT FROM AUTHOR]

Purpose: Keratinocytes are epithelial cells in epidermis tightly connected to each other by cell-cell junction. During the process of wound re-epithelization, these epithelial cells undergo significant phenotypic changes that are reminiscent of the EMT process occurring during development and tumor progression. As the wound healing progresses, the reepithelization is initiated by activation and migration of keratinocytes from the edges of the wound. As they migrate toward the wound center, keratinocytes set off from their laminin-rich niche, and are forced to experience the abrupt changes in ECM microenvironment consisting of fibronectin and collagen matrices with locally elevated stiffness along the interface of the blood clot and the granulation tissue layer. In this study, thus, we tried to elucidate the effect of alteration of ECM proteins and substrate stiffness in keratinocytes during wound re-epithelization. Methods: We expose primary normal human epidermal keratinocytes (NHEK) to the culture microenvironment, rich in fibronectin or collagen with varying stiffness, to investigate the role of the physiochemical stimuli on induction of EMTlike changes in NHEKs. Results: Our results show that a stiffer substrate coated with either fibronectin or collagen induces faster migration with elevated expressions of mesenchymal genes (vimentin, MMP1), and proteins (vimentin, FAK) while suppressing those of the epithelial origin (CK10, CK14, Fillagrin, and Ecadherin) when compared to the laminin coated surfaces. Conclusions: Various physicochemical stimuli inherently present at the wounds must orchestrate to induce the EMT process in NHEKs, promoting the re-epithelization. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor (HGF) induces cell migration and scattering by mechanisms that are thought to tip a local balance of competing physical forces; cell-to-cell and cell-to-substrate forces. In this local process, HGF is known to attenuate local cadherin-dependent adhesion forces for cell-cell junction development and enhance local integrin-dependent contractile forces for pulling neighboring cells apart. Here we use an expanding island of confluent Madin-Darby canine kidney (MDCK) cells as a model system to quantify the collective cell migration. In the absence of HGF, cell trajectories are highly tortuous whereas in the presence of HGF, they become far less so, resembling free expansion of a gas. At the level of cell-to-cell junctions, HGF attenuates the linkage of stress fibers to cell-to-cell junctions with concomitant decrease in intercellular stress. At the level of cell-to-substrate junctions, HGF augments the linkage of stress fibers to cell-to-substrate junctions with no apparent effect on traction. Together, HGF induces both structural changes in the actin-bound junctional protein complex and physical forces spanning multicellular clusters, which further promotes the expansion of confluent cellular layer. [ABSTRACT FROM AUTHOR]