Abstract:
:Integrins play myriad and vital roles in development and disease. They connect a cell with its surroundings and transmit chemical and mechanical signals across the plasma membrane to the cell's interior. Dissecting their roles in cell behavior is complicated by their overlapping ligand specificity and shared downstream signaling components. In principle, immobilized synthetic peptides can mimic extracellular matrix proteins by supporting integrin-mediated adhesion, but most short peptide sequences lack selectivity for one integrin over others. In contrast, synthetic integrin antagonists can be highly selective. We hypothesized that this selectivity could be exploited if antagonists, when immobilized, could support cellular adhesion and activate signaling by engaging specific cell-surface integrins. To investigate this possibility, we designed a bifunctional (RGD)-based peptidomimetic for surface presentation. Our conjugate combines a high affinity integrin ligand with a biotin moiety; the former engages the α(v)β(3) integrin, and the latter allows for presentation on streptavidin-coated surfaces. Surfaces decorated with this ligand promote both cellular adhesion and integrin activation. Moreover, the selectivity of these surfaces for the α(v)β(3) integrin can be exploited to capture a subset of cells from a mixed population. We anticipate that surfaces displaying highly selective small molecule ligands can reveal the contributions of specific integrin heterodimers to cell adhesion and signaling.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Klim JR,Fowler AJ,Courtney AH,Wrighton PJ,Sheridan RT,Wong ML,Kiessling LLdoi
10.1021/cb2004725subject
Has Abstractpub_date
2012-03-16 00:00:00pages
518-25issue
3eissn
1554-8929issn
1554-8937journal_volume
7pub_type
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