Understanding how the spatial distribution of adhesive ligands regulates cell behavior is crucial for designing biomaterials. This study investigates how precisely controlled ligand spacing affects cell spreading and integrin subtype engagement. Using engineered polyacrylamide hydrogels with gold nanoparticle arrays, we explored the impact of RGD ligand spacings (30 and 150 nm) on human mesenchymal stromal cells. Cells exhibited distinct morphological behaviors: smaller spacings promoted larger spreading areas, while larger spacings resulted in elongated shapes with reduced spreading. Mechanistically, we found that the α₅β₁ integrin, not the α_vβ₃ integrin, played a central role in mediating these responses, alongside lamellipodia formation. Our findings provide critical insights into the spatial sensing of ligands, highlighting the influence of ligand spacing on cellular mechanotransduction and integrin-specific responses. This work advances the understanding of cell-material interactions and offers potential strategies for designing biomaterials to guide cell behavior in tissue engineering.

中文翻译：

---

整合素亚型和板状伪足在细胞粘附过程中介导 RGD 配体的空间感应


了解粘附配体的空间分布如何调节细胞行为对于设计生物材料至关重要。本研究调查了精确控制的配体间距如何影响细胞扩散和整合素亚型结合。使用带有金纳米颗粒阵列的工程聚丙烯酰胺水凝胶，我们探索了 RGD 配体间距 （30 和 150 nm） 对人间充质基质细胞的影响。细胞表现出不同的形态行为：较小的间距促进较大的扩散面积，而较大的间距导致细长的形状和减少的扩散。从机制上讲，我们发现 α₅β₁ 整合素，而不是 α_Vβ₃ 整合素，与板状伪足一起在介导这些反应中起着核心作用。我们的研究结果为配体的空间感应提供了重要见解，突出了配体间距对细胞机械转导和整合素特异性反应的影响。这项工作促进了对细胞-材料相互作用的理解，并为设计生物材料以指导组织工程中的细胞行为提供了潜在策略。