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Imaging Cell Adhesion and Migration
Published in Margarida M. Barroso, Xavier Intes, In Vivo, 2020
Chandrani Mondal, Julie Di Martino, Jose Javier Bravo-Cordero
Studies of highly motile tumor cells have revealed that the formation of a leading-edge protrusion is the initial step of the motility cycle and is driven by actin polymerization. Different types of membrane protrusions at the leading edge have been described based on their shape (lamellipodia-flat shape, pseudopodia-round, filopodia-needle shape, lobopodia-cylindrical) (Taylor and Condeelis, 1979), and all of them contribute to the efficient movement of cells. The formation of these protrusions depends on the control of actin polymerization by actin regulatory molecules, such as cofilin, Arp2/3, and GTPases, such as RhoA, RhoC, and Rac1 (Bravo-Cordero et al., 2013a). Adhesion to the substrate during migration is mediated by focal adhesions, which are complex structures that anchor the cell to the extracellular matrix (Burridge, 2017). At these adhesion sites, clustering of integrin receptors transmits signals intracellularly to modulate cellular function. The first identification of these structures by electron microscopy comes from the studies of Abercrombie et al. (1971) in fibroblasts. Finally, retraction at the back of the cell through contraction mediates the translocation of the cell body (Figure 13.1a).
Emulating Biomechanical Environments in Microengineered Systems
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
Jason Lee, Lei Mei, Daniel Chavarria, Aaron B. Baker
The ECM is mainly composed of collagen fibers, proteoglycans, glycoproteins, and other matrix proteins, that bind to integrin receptors on cell surface to form cell–matrix attachments. Most human cells are adherent and must be anchored to an appropriate ECM to survive. The integrin family of receptors are capable of mediating signals from the ECM to regulate cellular behaviors, including proliferation, differentiation, and apoptosis (Giancotti and Ruoslahti 1999). As integrins bind to ECM and become activated, they become clustered and, in turn, interact with intracellular signaling molecules including focal adhesion kinase and Src. These signaling molecules lead to the formation of a focal adhesion (FA) which provides a connection to the actin cytoskeleton via linker proteins including talin, vinculin, filamin, and α-actinin (Humphrey, Dufresne, and Schwartz 2014). The activation and clustering of integrins also associated with RhoA activation, MAPK/ERK pathway signaling (Shyy and Chien 2002), and signaling through the Hippo signaling pathway (Dupont et al. 2011). Therefore, the mechanical properties of the matrix that cells adhere to can influence these integrin-elicited signaling events and are important in regulating various cell behaviors as well as processes such as regeneration, inflammation, and malignancy. In the following section, we will review current research methods and techniques for mimicking the mechanics of ECM and we will mainly focus on stiffness and topographical cues.
Cellular Response to Nanoscale Features
Published in Yubing Xie, The Nanobiotechnology Handbook, 2012
Manus J.P. Biggs, Matthew J. Dalby, Shalom J. Wind
The regulation of focal adhesion formation in adherent cells is highly complex and involves both the turnover of single integrins and the reinforcement of the focal adhesion plaque by protein recruitment. It follows that focal adhesions provide structural integrity and dynamically link the ECM to intracellular actin filaments (Figure 20.2), directly facilitating cell migration and spreading through continuous regulation and turnover of a diverse network of proteins. Furthermore, in combination with growth factor receptors, these macromolecular assemblies initiate complex signaling pathways and regulate the activity of nuclear transcription factors—processes crucial to cell growth, differentiation, and survival, as will be discussed.
Graphene oxide coated shell-core structured chitosan/PLLA nanofibrous scaffolds for wound dressing
Published in Journal of Biomaterials Science, Polymer Edition, 2020
Chengwei Yang, Zhiyong Yan, Yuan Lian, Jiayan Wang, Kuihua Zhang
The results of PIECs proliferation on different nanofibrous scaffolds and TCPS after 3 days culturing were shown in Figure 7. It was explicit that the PIECs proliferated significant on the GO-coated CS/PLLA nanofibrous scaffolds compared to those on the CS/PLLA nanofibrous scaffolds, in the meanwhile, the PIECs proliferation on CS/PLLA nanofibrous scaffolds had no significant difference in comparison with TCPS. The results clarified that both CS/PLLA and GO-coated CS/PLLA nanofibrous scaffolds had no cytotoxicity, and GO-coated CS/PLLA nanofibrous scaffolds even could promote the proliferation of PIECs. Thus may be traced from the surface chemistry and topographical structure of GO-coated CS/PLLA nanofibrous scaffolds. The coatings of GO nanosheets improved surface roughness, hydrophilicity and introduced bioactive functional groups (hydroxyl, carboxyl, and epoxy). It is reported that rougher surface enhanced the number of focal adhesions and cell proliferation. The focal adhesions are of fundamental importance in human physiology because they regulate cell adhesion, mechanical sensing and signal control of cell growth and differentiation [56]. Functional groups of GO promoted cell attachment and proliferation through increasing the combination of cell-adhesive proteins [57].
Highly stretchable HA/SA hydrogels for tissue engineering
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Chengcheng Zhu, Rui Yang, Xiaobin Hua, Hong Chen, Jumei Xu, Rile Wu, Lian Cen
In tissues that undergo shear and tensile stresses, collagen is usually arranged in highly organized fibrils [48]. That is, during those tissue development and maintenance, cells in these tissue are constantly subjected to mechanical stimulations and their synthesized collagen are then arranged. Cells adhere and interact with their substrate using integrins, focal adhesions and their ability to stimulate downstream signaling pathways. Such mechanotransduction signals conveyed to cells via their adhesion to the matrix also clearly regulate the development of various tissues and their maintenance of normal functionalities [48]. A normal tissue cell not only applies forces, but also responds through cytoskeleton organization to the resistance that the cell senses, regardless of whether the resistance derives from normal tissue matrix, synthetic substrate, or even an adjacent cell. It was thus suggested that mechanical properties of the substrate or scaffold can profoundly affect cell locomotion, growth, and differentiation [49–53]. Therefore, designing matrices with proper and controllable mechanical properties as those of load bearing tissues is becoming a focus point in regenerative medicine. The current developed HA/SA hydrogel, especially HA8/SA1, could be a promising candidate as a cellular carrier to withstand high tensile requirement.
Influence of Antimycin A, a bacterial toxin, on human dermal fibroblast cell adhesion to tungsten-silicon oxide nanocomposites
Published in Journal of Experimental Nanoscience, 2019
Hassan I. Moussa, Gyeongsu Kim, Jessica Tong, D. Moira Glerum, Ting Y. Tsui
The morphology and spreading characteristics exhibited by the human skin fibroblasts shown in Figures 3 and 4 strongly support a preferential adhesion for these cells to tungsten as compared to silicon oxide. Our results show elongated cells that are oriented parallel to the tungsten line axes, likely as a means to increase association with tungsten, and this cell behavior was dependent on line widths (Figure 7). A previously developed mathematical model [5, 28] has shown that such cell alignment pattern dependence is the result of preferential cellular adhesion to tungsten. Given that surface features on a substrate are known to alter the conformation of fibronectin [49], a critical extracellular matrix (ECM) protein that is expressed and secreted by fibroblasts in culture, which may be responsible for mediating the selective adhesion of the fibroblasts to the tungsten. Fibronectin is a well-characterized ECM protein that interacts with integrins in binding to substrates and promoting focal adhesions [49]. Moussa et al [5] have previously shown that monkey kidney epithelial (Vero) cells similarly align to tungsten/silicon oxide nanocomposite when cells are cultured in media containing FBS. However, when cells were cultured in an ultra-low protein medium, this cell alignment behavior degraded significantly, demonstrating that protein adsorption is an important contributing factor to the cell alignment characteristics. The adherence of corneal cells to silicon topographic features was also shown to be dependent on the presence of FBS in the culture media [4]. Ours is the first study to demonstrate that the morphology of human skin fibroblasts can be manipulated by using chemical-mechanical polished tungsten/silicon oxide nanocomposites.