Fractalkine targeting with a receptor-mimicking peptide-amphiphile.
In this study we have designed the NTFR peptide-amphiphile that mimics a fragment of the N-terminus of the fractalkine receptor (CX(3)CR1) and specifically targets fractalkine, a novel adhesion molecule expressed on the surface of inflamed endothelial cells. Bioartificial membranes were constructed from mixtures of NTFR peptide-amphiphiles and DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) phospholipids, and the affinity and specificity of fractalkine for the synthetic NTFR was investigated with an atomic force microscope (AFM). Fractalkine was immobilized onto the AFM tips, and forces were collected between fractalkine and the bioartificial membranes. The adhesive interactions were studied at the collective level, when each adhesion event corresponded to the rupture of multiple biomolecular bonds. Retraction force profiles for the fractalkine-NTFR system exhibited single or multiple peaks and a small percentage of the force curves demonstrated stretching of the fractalkine-NTFR complex. Strong adhesion was measured when both DPPC and NTFR were present, compared to pure NTFR surfaces. This may be due to the fact that the DPPC molecule is shorter, and thus it can provide more space for the peptide headgroup to bend and expose its sequence at the interface. Specificity was demonstrated by comparing the NTFR-fractalkine adhesion to the forces between the alpha(5)beta(1) integrin (an adhesion receptor expressed on the surface of endothelial cells) and other surfaces such as GRGDSP (the specific ligand for alpha(5)beta(1)), GRGESP (an inactive sequence), and NTFR.
Kokkoli
Efrosini
E
Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota 55455, USA. kokkoli@ cems.umn.edu
Kasinskas
Rachel W
RW
Mardilovich
Anastasia
A
Garg
Ashish
A
D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D018716:Molecular Mimicry; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000737:chemistry / Q000378:metabolism*; D015728:Receptors, HIV / Q000737:chemistry / Q000378:metabolism*; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism*
D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D010446:Peptide Fragments; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D013501:Surface-Active Agents