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Phototriggered cell attachment and detachment

The ability to trigger or turn ‘on/off’ material properties with external stimuli in order to control biological responses is critically important to biotechnological and biomedical applications. One such application is the use of light to trigger cell adhesion to synthetic materials by controlling the presentation of the bioadhesive arginine-glycine-aspartic acid (RGD) oligopeptide. Using a photocleavable caged RGD peptide we have been able to photoactivate cell adhesion to artificial surfaces. Cell patterns onto different substrates were obtained, where cell attachment is only driven by the presence of the photoactivated RGD. This approach is now being used for more profound studies of cell adhesion phenomena.

Caged cell adhesive peptide: the photoremovable group 3-(4,5-dimethoxy-2-nitrophenyl)-2-butyl ester was introduced at the aspartate unit of cyclo(RGDfK), a very active and selective ligand of integrin aVb3. In the caged form the peptide is not recognized by integrins. After irradiation, the activity is restored. QCM-D shift of frequency (bold lines) and dissipation on crystals modified with cyclo[RGD(DMNPB)fK] and cyclo(RGDfK) demonstrating different affinity of the integrins for the caged and uncaged derivatives. Crystals were first loaded with integrin, followed by a washing step, an irradiation step and a second loading of integrin.



Novel linkers with an intercalated photocleavable group allowed us to revert the cell adhesion process by un-tethering the surface attached RGD peptide from the surface and releasing adhering cells upon light exposure. This is the firs light-based approaches able to specifically promote cell adhesion to materials with the ability to precisely de-activate or detach the cells at later time points or spatial locations. This is a relevant issue in cell biology (cells need to be removed from the culture plate during culture and before application) and tissue engineering (i.e. cell sheet engineering therapies). Our strategy is applicable to any material, provided proper linker design, and provides direct control over the molecular interactions involved in cell adhesion.



Phototriggered cell detachment from surfaces modified with a photocleavable linker


References:

  1. Photoactivatable caged cyclic RGD peptide for triggering integrin binding and cell adhesion to surfaces, M. Wirkner, S. Weis, V. San Miguel, M. Álvarez, R. A. Gropeanu, M. Salierno, A., R.E. Unger, C.J. Kirkpatrick, A. del Campo, ChemBioChem (2011) doi: 10.1002/cbic.201100437
  2. Triggered Cell Release from Materials using Bioadhesive Photocleavable Linkers, M. Wirkner, J. M. Alonso, V. Maus, M. Salierno, T. T. Lee, A. J. García, A. del Campo*, Advanced Materials (2011), 23: 3907–3910. doi: 10.1002/adma.201100925
  3. Phototriggering of cell adhesion by caged cyclic RGD peptides, S. Petersen, J. M. Alonso, A. Specht, P. Duodu, M. Goeldner, A. del Campo*, Angew. Chem. Int. Ed., 47, 3192-3195 (2008)



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