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A Photoactivatable α 5 β 1 ‐Specific Integrin Ligand
Author(s) -
Nair Roshna V.,
Farrukh Aleeza,
del Campo Aránzazu
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800180
Subject(s) - integrin , ligand (biochemistry) , chemistry , biophysics , covalent bond , click chemistry , cell , microbiology and biotechnology , biochemistry , receptor , combinatorial chemistry , biology , organic chemistry
The integrin α 5 β 1 is overexpressed in colon, breast, ovarian, lung and brain tumours, and has been identified as key component in mechanosensing. In order to study how dynamic changes in α 5 β 1 engagement affect cellular behaviour, photoactivatable derivatives of α 5 β 1 ‐specific ligands are presented in this article. A photoremovable protecting group (PRPG) was introduced into the ligand structure at a relevant position for integrin recognition. The presence of the chromophore temporarily inhibited ligand bioactivity. Light exposure at a cell‐compatible dose efficiently cleaved the protecting group and restored functionality. The photoactive ligand had an azide end‐functional group for covalent immobilisation onto biomaterials by click chemistry. Selective cell responses (attachment, spreading, migration) to the activated ligand on the surface are achieved by controlled exposure to light, at similar levels to the native ligand. Spatial and temporal control of the cellular response is demonstrated, including the possibility of in situ activation. Photoactivatable integrin‐selective ligands in model microenvironments will allow the study of cellular behaviour in response to changes in the activation of individual integrins as consequence of dynamic variations in matrix composition.