Cooperative effects of fibronectin matrix assembly and initial cell-substrate adhesion strength in cellular self-assembly.
Cooperative effects of fibronectin matrix assembly and initial cell-substrate adhesion strength in cellular self-assembly.
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DOI：
10.1016/j.actbio.2015.12.032
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发表时间：
2016-03-01
影响因子：
9.7
通讯作者：
Hocking DC
中科院分区：
文献类型：
--
作者：
Brennan JR;Hocking DC
细胞间纤维连接蛋白纤维的细胞依赖性聚合可以刺激细胞自组装成多细胞结构。支持纤维连接蛋白介导的细胞自组装的局部物理线索在很大程度上是未知的。在这里，纤维连接蛋白基质类似物被用作合成的粘连底物来模拟具有不同的整合素结合特异性、亲和力和/或密度的细胞-基质纤维连接蛋白纤维。我们利用这个模型来定量评估细胞-底物相互作用产生的粘附力和纤维连接蛋白原纤维组装诱导细胞自组装的能力之间的关系。结果表明，初始的而不是成熟的细胞-底物附着的强度与底物支持纤维连接蛋白介导的细胞自组装的能力相关。细胞对可溶性纤维连接蛋白的反应是双峰的，与底物的整合素结合特异性无关；增加超过临界阈值的可溶性纤维连接蛋白水平可以增加允许底物上的聚集性。一旦聚集体形成，持续的纤维连接蛋白聚合是维持凝聚力所必需的。在自组装过程中，可溶性纤维连接蛋白通过一种Rho依赖的机制降低细胞-基质黏附强度并诱导聚集性凝聚力，这表明细胞-细胞内纤维连接蛋白原纤维与细胞-基质黏附性之间的收缩力量的平衡控制着自组装和聚集性。因此，初始的细胞-底物附着强度可以为在各种底物上建立纤维连接蛋白介导的微组织制造的预测模型提供一个定量的基础。
The cell-dependent polymerization of intercellular fibronectin fibrils can stimulate cells to self-assemble into multicellular structures. The local physical cues that support fibronectin-mediated cellular self-assembly are largely unknown. Here, fibronectin matrix analogs were used as synthetic adhesive substrates to model cell-matrix fibronectin fibrils having different integrin-binding specificity, affinity, and/or density. We utilized this model to quantitatively assess the relationship between adhesive forces derived from cell-substrate interactions and the ability of fibronectin fibril assembly to induce cellular self-assembly. Results indicate that the strength of initial, rather than mature, cell-substrate attachments correlates with the ability of substrates to support fibronectin-mediated cellular self-assembly. The cellular response to soluble fibronectin was bimodal and independent of the integrin-binding specificity of the substrate; increasing soluble fibronectin levels above a critical threshold increased aggregate cohesion on permissive substrates. Once aggregates formed, continuous fibronectin polymerization was necessary to maintain cohesion. During self-assembly, soluble fibronectin decreased cell-substrate adhesion strength and induced aggregate cohesion via a Rho-dependent mechanism, suggesting that the balance of contractile forces derived from fibronectin fibrils within cell-cell versus cell-substrate adhesions controls self-assembly and aggregate cohesion. Thus, initial cell-substrate attachment strength may provide a quantitative basis with which to build predictive models of fibronectin-mediated microtissue fabrication on a variety of substrates.