Max Planck Institute for Medical Research, Department of Cellular Biophysics, Jahnstraße 29, Heidelberg, 69120, Germany.
University of Foggia, Department of Clinical and Experimental Medicine, viale Pinto 1, Foggia, 71122, Italy.
Biomaterials. 2021 Jan;267:120484. doi: 10.1016/j.biomaterials.2020.120484. Epub 2020 Oct 26.
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 nanolithography and azide-functionalized integrin ligands (cyclic-RGD peptides or αβ 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 αβ integrin selective ligands. Moreover, iBMP-2 copresented with αβ integrin ligands induces the recruitment of αβ integrins in FAs. When copresented with RGD, iBMP-2 induces the assembly of a higher number of FAs, which are not affected by αβ integrin blocking. Our dual-functionalized 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.
在这里，我们展示了通过表面纳米图案化将共价固定的 BMP-2 和整合素选择性配体用于确定它们在调节细胞黏附和焦点黏附组装中的相互作用特异性。通过嵌段共聚物胶束纳米光刻制备了携带单个 BMP-2 二聚体的金纳米粒子阵列，并通过点击化学将叠氮功能化整合素配体（环状-RGD 肽或 αβ 整合素模拟肽）固定在周围的聚乙二醇炔上。与添加到培养基中的 BMP-2 相比，表面固定的 BMP-2（iBMP-2）有利于黏附簇的空间分离，并增强了黏附于 αβ 整合素选择性配体的细胞中的焦点黏附（FA）大小。此外，iBMP-2 与 αβ 整合素配体共呈现会诱导 αβ 整合素在 FA 中的募集。当与 RGD 共呈现时，iBMP-2 会诱导形成更多的 FA，而这些 FA 不会受到 αβ 整合素阻断的影响。我们的双功能化平台提供了研究整合素和 BMP 受体之间串扰的可能性，并且更一般地说，它们可用于解决生物仿生表面上生长因子和黏附受体串扰的空间调节问题。
