Control of Cell Adhesion

Culturing of eukaryotic cells is an important element of modern life science. Although there are cells that can grow in free suspension, most cells derived from solid tissues need to be cultured at surfaces and must subsequently be lifted off for further use. Common protocols require the use of digesting enzymes like trypsin for this step, which will destroy any features outside the cell membrane. Hence, with these methods, harvesting of completely intact cells is impossible. Therefore, it was an attractive idea to apply smart polymer surfaces for the control of cell adhesion. 

There have been several approaches, utilizing stimuli such as electrochemistry, light, or temperature. As a consequence of the large size of cells, even mechanical deformation can be employed as switching stimulus. 

Yousaf and coworkers used an OEG-based surface bearing hydroquinone groups for electrochemical control of cell adhesion [186]. The hydroquinone groups were electrochemically converted into quinones, to which a cyclopentadienyl-modified RGD motif was then coupled via a Diels-Alder reaction. Although the hydroquinone-bearing surface was cell-repellent, fibroblasts attached to the areas 

Kessler and coworkers immobilized RGD peptides to a PMMA surface via a spacer incorporating an azobenzene unit [ 187]. The molecules were arranged in such a way that the RGD motifs were accessible to cells approaching the surface when the azo unit was in the E-form, and were hidden from the cells when the azo unit was in the Z-form. This enabled the reversible modulation of mouse osteoblast adhesion by irradiation with visible or UV light. However, the difference between on and off states is not very pronounced. Possibly, the accessibility of the RGD motif is not 

Recently, coatings composed of thermoresponsive side chain OEGs were employed for this purpose (Fig. 14) [44, 45], They offer the advantage of a better inherent biocompatibility than PNIPAM, show reduction of nonspecific protein adsorption even above the LCST, and exhibit effective control of cell adhesion by reducing the temperature from 37 to 25°C [191], 

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Boettner, B., and Van Aelst, L. (2009). Control of cell adhesion dynamics by Rapl signaling. Curr Opin Cell Biol 21 684-693. 

Cell surface-bound mucins can be involved in cell adhesion and also in the prevention of cell adhesion. For example, mucins participate in the control of cell adhesion mediated by integrin and E-cadherin. Some of these mucins are shed from the cell surface and are found in the bloodstream where they can play a role in the control of the immune system. For example, MUCl from breast cancer cells is shed and can be isolated from the serum. Depending on the nature of the mucins, they can block natural killer cell-mediated cell lysis and the action of cytotoxic lymphocytes. In cancer and other diseases affecting the epithelium, mucin gene expression is often altered. Especially, MUCl mucin is highly expressed on tumorigenic ductal epithelial cells. 

Tsuda Y, Kikuchi A, Yamato M et al (2004) Control of cell adhesion and detachment using temperature and thermoresponsive copolymer grafted culture surfaces. J Biomed Mater Res A 69 70-78... 

Another typical photoresponsive material for preparation of switchable surfaces is the spiropyran-merocyanine system. The spiropyran isomerizes to zwitterionic merocyanine conformation by UV exposure, and the reverse reaction can be triggered by irradiation with visible light as well as azobenzene. The changes in hydrophilic/hydrophobic properties through the isomerization of spiropyran groups also enable the control of cell adhesion/ detachment. Edahiro et al. reported photoresponsive cell culture substrates grafted... 

FIGURE 5.5.3 Control of cell adhesion on photoresponsive surfaces, (a) Access control of GRGDS peptides for biospecific cell adhesion by photoinduced cis-trans Isomerization of terminal azobenzene residues in grafted polymers (54). 

Edahiro, J. Sumaru, K. Tada, Y Ohi, K. Takagi, T. Kameda, M. Shinbo, T. Kanamori, T. Yoshuni, Y. In situ control of cell adhesion using photoresponsive culture surface. Biomacromolecules 2005, 6, 970-974. 

Zheng W, Zhang W, Jiang X. Precise control of cell adhesion by combination of surface chemistry and soft lithography. Adv Healthc Mater 2013 2(1) 95—108. 

For tile fabrication of interfaces with precise control of cell adhesion, the NITEC conjugation protocol was combined with the resistance of poly(oligoethylene glycol methyl ether metiiacrylate) (poly(MeOEGMA)) brushes and the versatility of bioinspired PDA surfaces (see Figure 9.7). 

Xu, F. J., Zhong, S. P, Yung, L. Y, Kang, E. T., Neoh, K. G. (2004). Surface-active and stimuli-responsive polymer-Si(lOO) hybrids from surface-initiated atom transfer radical polymerization for control of cell adhesion. Biomacromolecules, 5, 2392-2403. 

Xu, F.J., Zhong, S.P., Yung, L.Y.L., Kang, E.T., Neoh, K.G. 2004. Surface-Active and Stimuli-Responsive Polymer-Si(lOO) Hybrids from Surface-Initiated Atom Transfer Radical Polymerization for Control of Cell Adhesion. 

Edahiro, J. et al. (2005) In situ control of cell adhesion using photoresponsive culture surface. Biomacromolecules, 6, 970-974. 

B. Geiger, O. Ayalon, D. Ginsberg, T. Volberg, J. L. Rodriguez Fernandez, Y. Yarden, A. Ben-Ze ev, Cytoplasmic Control of Cell Adhesion, Cold Spring Harbor Symposia on Quant. Biol. 57 (1992) 631. 

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