Surface Co-presentation of BMP-2 and integrin selective ligands at the nanoscale favors α5β1 integrin-mediated adhesion

Here we present the use of surface nanopatterning of covalently immobilized BMP-2 and integrin selective ligands to determine the specificity of their interactions in regulating cell adhesion and focal adhesion assembly. Gold nanoparticle arrays carrying single BMP-2 dimers are prepared by block-copolymer micellar nano lithography and azide-functionalized integrin ligands (cyclic-RGD peptides or alpha(5)beta(1) integrin peptidomimetics) are immobilized on the surrounding polyethylene glycol alkyne by click chemistry. Compared to BMP-2 added to the media, surface immobilized BMP-2 (iBMP-2) favors the spatial segregation of adhesion clusters and enhances focal adhesion (FA) size in cells adhering to alpha(5)beta(1) integrin selective ligands. Moreover, iBMP-2 copresented with alpha(5)beta(1) integrin ligands induces the recruitment of alpha(v)beta(3) integrins in FAs. When copresented with RGD, iBMP-2 induces the assembly of a higher number of FAs, which are not affected by alpha(5)beta(1) integrin blocking. Our dualfunctionalized platforms offer the possibility to study the crosstalk between integrins and BMP receptors, and more in general they could be used to address the spatial regulation of growth factors and adhesion receptors crosstalk on biomimetic surfaces.

Automated summary

This study investigates the specificity of interactions between BMP-2 and integrin selective ligands using surface nanopatterning, revealing that immobilized BMP-2 enhances cell adhesion and focal adhesion assembly, and induces the recruitment of different integrins in FAs. The dual-functionalized platforms offer the potential to study crosstalk between integrins and BMP receptors.