Light-Controlled Promiscuous Cell Adhesion through the Plasma Membrane-Binding Protein BcLOV4.

Movement Directionality in Collective Migration of Germ Layer Progenitors

Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation

Mammalian tissues and organs are composed of different types of cells that adhere to each other homotypically (i.e. interactions between cells of the same cell type) or heterotypically (i.e. interactions between different cell types), forming a variety of cellular patterns, including mosaic patterns. At least three types of cell-cell adhesion have been observed: symmetric homotypic, asymmetric homotypic and heterotypic cell adhesions. Cadherins and nectins, which are known cell-cell adhesion molecules, mediate these cell adhesions. Cadherins comprise a family of more than 100 members, but they are primarily involved in homophilic trans-interactions (i.e. interactions between the same cadherin members) between opposing cells. By contrast, the nectin family comprises only four members, and these proteins form both homophilic and heterophilic trans-interactions (i.e. interactions between the same and different nectin members on opposing cells). In addition, heterophilic trans-interactions between nectins are much stronger than homophilic trans-interactions. Because of these unique properties, nectins have crucial roles in asymmetric homotypic cell-cell adhesion at neuronal synapses and in various types of heterotypic cell-cell adhesions. We summarize recent progress in our understanding of the biology of nectins and discuss their roles in heterotypic cell-cell adhesions, whose formation cannot be solely explained by the action of cadherins.

Chapter 3 - Scaffold-based stem cells tissue graft

Reconstructing nanofibers from natural polymers using surface functionalization approaches for applications in tissue engineering, drug delivery and biosensing devices

It is widely accepted that cell surface macromolecules must mediate recognition phenomena that allow like cells within a tissue to adhere to one another (homotypic adhesion) as well as to cells of other types (heterotypic adhesion). These macromolecular interactions occur by multistep processes that are important in the formation and maintenance of tissues both in the adult organism and during embryonic development. Moreover, we now know that specific cell-cell interactions regulate many physiological processes. Contact inhibition of growth is a well-documented example of negative growth regulation induced by homotypic cellular adhesions. Cellular motility may also be regulated in a negative sense as observed in the phenomenon of contact inhibition of motion. And highly specific intercellular adhesions can induce the syntheses of enzymes and proteins responsible for the expression of tissue-specific traits.

Rho-associated protein kinase (ROCK), a molecular switch, modulates cellular functions in many cancers, such as hepatocellular, breast, colon cancers, etc. However, little is known the effect of ROCK on cell adhesion and mobility in esophageal squamous cell cancer (ESCC), one of the most diagnosed cancers in China. In this study, Y-27632 was used to specifically block ROCK activity in ESCC cells. Adhesion of ESCC cells was detected by homotypic and heterotypic adhesion assay together with examination of E-cadherin expression. Motility of ESCC cells changes were examined by detection of phosphorylated cofilin and observed under confocal microscopy, respectively. We found that Y-27632 increased both heterotypic and homotypic adhesion, and the expression of E-cadherin; decreased phosphorylated cofilin resulting in actin rearrangement in ESCC cells. All these findings indicate that ROCK signaling pathway plays an important role in cell adhesion and mobility, suggesting that it may be used as a potential target for therapy of ESCC.

Intercellular interaction has tremendous impacts on physiological processes, while unsuccessful cell-cell interaction causes diseases, such as tumorigenesis and metastasis. In-depth investigation of cell-cell adhesions is of great significance to understand the pathological state of cells, and for the rational design of drugs and therapies. Herein, we developed a force-induced remnant magnetization spectroscopy (FIRMS) method to measure cell-cell adhesion in a high throughput way. Our results showed that FIRMS is capable of quantifying and identifying cell-cell adhesion with high detection efficiency. Specifically, we quantified homotypic and heterotypic adhesion forces during tumor metastasis using breast cancer cell lines. We observed that homotypic and heterotypic adhesion forces of cancer cells were associated with degrees of malignancy. In addition, we revealed that CD43-ICAM-1 was a ligand-receptor pair mediating heterotypic adhesion of breast cancer cells to endothelial cells. These findings contribute to advance in-depth understanding of the process of cancer metastasis and provide insight into targeting intercellular adhesion molecules as a potential strategy to inhibit cancer metastasis.

Human hair is a potential biomaterial for biomedical applications. Improper disposal of human hair may pose various adverse effects on the environment and human health. Therefore, proper management of human hair waste is pivotal. Human hair fiber and its derivatives offer various advantages as biomaterials such as biocompatibility, biodegradability, low toxicity, radical scavenging, electroconductivity, and intrinsic biological activity. Therefore, the favorable characteristics of human hair have rendered its usage in tissue engineering (TE) applications including skin, cardiac, nerve, bone, ocular, and periodontal. Moreover, the strategies by utilizing human hair as a biomaterial for TE applications may reduce the accumulation of human hair. Thus, it also improves human hair waste management while promoting natural, environmental-friendly, and nontoxic materials. Furthermore, promoting sustainable materials production will benefit human health and well-being. Hence, this article reviews and discusses human hair characteristics as sustainable biomaterials and their recent application in TE applications. Impact Statement This review article highlights the sustainability aspects of human hair as raw biomaterials and various elements of human hair that could potentially be used in tissue engineering (TE) applications. Furthermore, this article discusses numerous benefits of human hair, highlighting its value as biomaterials in bioscaffold development for TE applications. Moreover, this article reviews the role and effect of human hair in various TE applications, including skin, cardiac, nerve, bone, ocular, and periodontal.

Research on tissue engineering has been actuated for want of improved treatments and has now come out as a likely alternative to organ transplantation. The two indispensable components for regeneration of tissues are cells and scaffolds. Stem cells are undifferentiated cells that have proliferative capacity and the ability to differentiate into specific mature lineages, which is called plasticity. The physical and chemical signals from the surrounding microenvironment can influence the proliferation as well as the differentiation of stem cells into more specialized cell types and thus play an important role regulating the fate of the stem cells. Over decades, scientists have revealed that the stem cells' growth and differentiation can be stimulated and regulated by scaffold properties. Silk fibroin has been used in both in vitro and in vivo tissue engineering applications and has shown promising results, particularly for bone tissue engineering applications. For successful application of stem cells in tissue engineering, directed differentiation of stem cells will have to include approaches that not only regulate cell-fate specification but also cell maturation to access a complete range of cell types and stages. One of the ways of achieving this is by modifying the surface properties of the scaffold to have control over the stem cell behavior and final product. In this spotlight on application, we recapitulate the current developments of silk-based materials and their surface modifications for patterning of cells and stem cell differentiation with a focus on bone tissue engineering.

Tissue engineering has recently become an effective method for restoring and rebuilding injured tissues and organs. Scaffolds for tissue engineering are essential because they not only give targeted cells structural support, but also act as templates to direct regeneration of tissue and regulate structure of tissue. Nanomaterials of various types have gradually grown and attracted a wide spectrum of research interests over the previous few years due to their distinctive physicochemical properties and exceptional biocompatibility, allowing remarkable advancements in the repair of wounds, wound healing, regeneration of neural tissue, and cardiac tissue engineering. This chapter focuses on the most recent different types of nanomaterials, its synthesis method, functionalisation and characterisation method for the different application in tissue regeneration and engineering. The chapter also focusses on the developments in the usage of scaffolds, nanosheets, or hydrogels based on different nanomaterials that are designed to repair cartilage, bone, and skin tissues. We have also summarised the difficulties and potential of nanomaterial applications in tissue engineering.

Cytoskeletal regulation of cell adhesion is vital to the organization of multicellular structures. The focal adhesion protein zyxin emerged as a key regulator of actin assembly because zyxin recruits Enabled/vasodilator-stimulated phospho-proteins (Ena/VASP) to promote actin assembly. Zyxin also localizes to the sites of cell-cell adhesion and is thought to promote actin assembly with Ena/VASP. Using shRNA targeted to zyxin, we analyzed the roles of zyxin at adhesive contacts. In zyxin-deficient cells, the actin assembly at both focal adhesion and cell-cell adhesion was limited, but their migration rate was unchanged. Cell spreading on E-cadherin-coated surfaces and the formation of cell clusters were slower for zyxin-deficient cells than wild type cells. By ablating a single cell within a cell monolayer, we quantified the rate of wound closure driven by a contractile circumferential actin ring. Zyxin-deficient cells failed to recruit VASP to cell-cell junctions at the wound edge and had a slower wound closure rate than wild type cells. Our results suggest that, by recruiting VASP, zyxin regulates actin assembly at the sites of force-bearing cell-cell adhesion.

Loss of cell-matrix adhesion is often associated with acute epithelial injury, suggesting that "anoikis" may be an important contributor to cell death. Resistance against anoikis is a key characteristic of transformed cells. When nontransformed epithelia are injured, activation of the epidermal growth factor (EGF) receptor (EGFR) by paracrine/autocrine release of soluble ligands can induce a prosurvival program, but there is generally evidence for concomitant dedifferentiation. The EGFR ligand, heparin-binding EGF-like growth factor (HB-EGF), is synthesized as a membrane-anchored precursor that can activate the EGFR via juxtacrine signaling or can be released and act as a soluble growth factor. In Madin-Darby canine kidney cells, expression of membrane-anchored HB-EGF increases cell-cell and cell-matrix adhesion. Therefore, these studies were designed to test the effects of juxtacrine HB-EGF signaling upon cell survival and epithelial integrity when cells are denied proper cell-matrix interactions. Cells expressing a noncleavable mutated form of membrane-anchored HB-EGF demonstrated increased survival from anoikis, formed larger cell aggregates, and maintained epithelial characteristics even following prolonged detachment from the substratum. Physical association between membrane-anchored HB-EGF and EGFR was observed. Signaling studies indicated synergistic effects of EGFR activation and phosphatidylinositol 3-kinase signaling to regulate apoptotic and survival pathways. In contrast, although administration of exogenous EGF partially suppressed anoikis in wild type cells, it also led to an increased expression of mesenchymal markers, suggesting dedifferentiation. Taken together, we propose a novel role for membrane-anchored HB-EGF in the cytoprotection of epithelial cells.

Personalized hydrogels for individual health care: preparation, features, and applications in tissue engineering

The characteristics of tissue engineered scaffolds are major concerns in the quest to fabricate ideal scaffolds for tissue engineering applications. The polymer scaffolds employed for tissue engineering applications should possess multifunctional properties such as biocompatibility, biodegradability and favorable mechanical properties as it comes in direct contact with the body fluids in vivo. Additionally, the polymer system should also possess biomimetic architecture and should support stem cell adhesion, proliferation and differentiation. As the progress in polymer technology continues, polymeric biomaterials have taken characteristics more closely related to that desired for tissue engineering and clinical needs. Stimuli responsive polymers also termed as smart biomaterials respond to stimuli such as pH, temperature, enzyme, antigen, glucose and electrical stimuli that are inherently present in living systems. This review highlights the exciting advancements in these polymeric systems that relate to biological and tissue engineering applications. Additionally, several aspects of technology namely scaffold fabrication methods and surface modifications to confer biological functionality to the polymers have also been discussed. The ultimate objective is to emphasize on these underutilized adaptive behaviors of the polymers so that novel applications and new generations of smart polymeric materials can be realized for biomedical and tissue engineering applications.