Cell-adhesion

FIGURE 8.15 Cross section of the fight-addressable potentiometer sensor (LAPS) chip integrated with a flow channel for study of adherent cells [848]. Reprinted with permission from the Institute of Electrical Engineers of lapan. 

Various types of adherent cells were grown on a coverslip, which was then laid on top of the LAPS chip. Measurements were made for acidification of (1) normal human epidermal keratinocytes stimulated by epidermal growth factor (EGP) or organic chemicals, and of (2) human uterine sarcoma cells as a response to doxorubicin and vincristine (chemotherapeutic drugs). In addition, the inhibition (by ribavirin) of the viral infection of murine fibroblastic L cells by vesicular stomatitis virus (VSV) was investigated by following the acidification rate. A limitation of these studies is the requirement for a low-buffered medium (low bicarbonate content) to achieve maximum sensitivity [847]. 

In another report, the release of cytochrome c from mitochondria to cytosol in neuroblastoma-glioma hybrid cells was studied on a quartz chip. The released cytochrome c was measured by scanning thermal lens microscopy [851]. 

In one report, cell growth of chicken embryo spinal cord neurons was studied. These neuron cells have been deposited in a micromachined Si chip coated with a synthetic additive protein (polylysine). It was found that groups of neurites grew towards the channel (50 im wide) connecting between pits where the neurons were deposited [856]. 

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Cell Adhesion. The membranes of leukocytes and platelets contain a variety of components that promote ceU-surface contact. Although numerous ceU-surface molecules are likely to play a role in ceU-surface adhesion, the group of selectins are of particular interest to research on this subject. Selectins are molecules that are known to promote leukocyte—platelet adhesion. However, selectin-based models have not been able to account for the fact that platelets are allowed to pass through the filter and leukocytes are not. 

Chothia, C. Jones, E.Y. The molecular structure of cell adhesion molecules. Annu. Rev. Biochem. 66 823-862, 1997. 

Kemler, R. (1993). From cadherins to catenins Cytoplasmic protein mreracrions and reglnrion of cell adhesion. Trends Genet. 9(9), 317-321. 

Extracellular matrix The surfaces of animal cells are covered with a flexible and sticky layer of complex carbohydrates, proteins, and lipids. This complex coating is cell-specific, serves in cell-cell recognition and communication, creates cell adhesion, and provides a protective outer layer. 

The largest numbers of integrins are members of the (31 integrins, also known as the very late antigen (VLA) subfamily because of its late appearance after activation. There are at least seven receptors characterized from this subfamily, each with different ligand specificity. Among the most studied include the 04(31 and a5 31 receptors. The leukocyte integrin a4 31 is a cell adhesion receptor that is predominantly expressed on lymphocytes, monocytes and eosinophils. 

AQPO, formerly known as the Major Intrinsic Protein of 26 kDa (MDP26), is specifically expressed in the plasma membrane of eye lens fiber cells. It transports water to a low degree, but has also been implicated in cell adhesion and gap junction formation. Its main role is to maintain the transparency of the lens by maintaining a tight cellular connection to neighboring cells and/or by controlling the fluid circulation. 

The basement membrane is a structure that supports overlying epithelial or endothelial cells. The primary fimction of the basement membrane is to anchor down the epithelium to its loose connective tissue underneath. This is achieved by cell-matrix adhesions through cell adhesion molecules. 

Cadherins are a superfamily of Ca2+-sensitive cell-cell adhesion molecules, which cause homophilic cell interactions. Cadherins can be divided into different subfamilies, namely, classical cadherins, desmosomal cadherins, protocadherins, and nonconventional cadherins (7TM cadherins, T-cadherin, FAT). Classical cadherins are often denoted by a prefix reflecting their principal expression domains e.g., E is epithelial, N is neuronal, and P is placental. However, this classification is not stringent, as for instance E-cadherin can also be found in certain neuronal tissues, and N-cadherin is also found in epithelial cells. Among the desmosomal cadherins, two subfamilies can be distinguished the desmocollins 1-3 and the desmogleins 1-4. 

The extracellular domain of cadherins consists of a variable number of a repeated sequence of about 110 amino acids. This sequence is termed the cadherin repeat and resembles in overall structure, but not in sequence, the Ig like domains. The cadherin repeat is the characteristic motive common to all members of the cadherin superfamily. Classical and desmosomal cadherins contain five cadherin repeats, but as many as 34 repeats have been found in the FAT cadherin (see below). Cadherins are calcium-dependent cell adhesion molecules, which means that removal of Ca2+, e.g., by chelating agents such as EDTA, leads to loss of cadherin function. The Ca2+-binding pockets are made up of amino acids from two consecutive cadherin repeats, which form a characteristic tertiary structure to coordinate a single Ca2+ion [1]. 

The classical cadherins are translated as precursor because they are N-terminally cleaved to reveal the mature proteins. This processing is required to activate the cell adhesion function of cadherins. Cadherins interact in trans (i.e., from opposite cells) via the most N-terminal cadherin rqDeats. A short amino acid sequence within this repeat, histidine-alanine-valine (HAV), has been implicated in mediating cell-cell contacts as HAV peptides can disrupt cadherin-dependent cell adhesion. Besides the trans-interactions of cadherins, the extracellular domains are also capable of forming cis-dimers through lateral amino acid contacts between cadherin molecules on one cell. This dimerization again mainly involves the first cadherin repeat. A zipper model based on the pattern of alternating cis- and trans-dimers [1] for the adhesive interactions has been proposed. 

Integrins, selectins, cadherins, claudins and other cell adhesion molecules are involved in the interaction of cells with other cells or with extracellular matrix components. Some of them also serve as receptors by inducing outside-in or additional inside-out signaling. 

A process by which epithelal cells lose cell-cell adhesion and become more migratory and acquire mesenchymal properties. The process is associated with... 

The leukocyte integrin a 4(3 1 (also known as VLA-4 and CD49d/CD29) is a cell adhesion receptor, which is predominantly expressed on lymphocytes, monocytes and eosinophils. VLA-4 is generally selective for the CS1 domain within fibronectin, with an essential requirement for LDV sequence for binding. VLA-4 also binds to VCAM-1 as a counter receptor. 

Integrins constitute a large family of a (3 heterodimeric cell surface, transmembrane proteins that interact with a large number of extracellular matrix components through a metal ion-dependent interaction. The term integrin reflects their function in integrating cell adhesion and migration with the cystoskeleton. 

GPI-anchored proteins constitute a quite diverse family of cell-surface molecules that participate in such processes as nutrient uptake, cell adhesion, and membrane signaling events [3]. All GPI-linked proteins are destined for the cell surface via trafficking through the secretory pathway, where they acquire the... 

Ras is a G protein that cycle between two conformations, an activated Ras-GTP or inactivated form Ras-GDP. Ras, attached to the cell membrane by lipidation, is a key component in many signalling cascades, which couple growth factor receptors to downstream effectors that control such processes as cytoskeletal integrity, proliferation, cell adhesion, apoptosis and cell migration. Mutations and dysregulations of the Ras protein leading to increased invasion and metastasis, and decreased apoptosis are very common in cancers. 

Cell Adhesion Molecules Cell-cycle Arrest Cell Cycle Checkpoints Cell Cycle Control Cell Division Cycle Cell Multiplication Cell Proliferation Cellular Immmunity Central Core Disease (CCD)... 

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