Interfacial migration is central to multiple processes including morphogenesis and wound healing. However, the sensitivity of interfacial migration to properties of the interfacial microenvironment has not been adequately explored. Here, we address this question by tracking motility of 3T3 fibroblasts at the interface of two hydrogels. By sandwiching cells between two adhesive gels (composed of methacrylated gelatin) or between an adhesive and a non-adhesive gel (composed of gellan), we show that cells are more motile in case of the latter. By tuning the bulk stiffness of the gellan gel, we then show that motility is tuned in a stiffness-dependent manner. Fastest motility observed in case of the stiffest gel was associated with increased cell height, suggestive of stiffness-mediated cytoskeletal assembly. Inhibition of cell motility by contractile agonists and actin depolymerizing drugs is indicative of a mode of migration wherein cells combine contractile tractions exerted at their base and actin-based pushing forces on the top surface to propel themselves forward. Together, our results suggest that dorso-ventral adhesion anisotropy and stiffness can be collectively tuned to engineer interfacial migration.

Statement of Significance

It is increasingly understood that cells migrate in vivo through confining spaces which typically occur as pores in the matrix and through naturally occurring interfaces that exist between neighbouring ECM fibers, or between the stroma and the vasculature. Such interfaces are also created when treating wounds on the skin surface by covering the wounds with adhesives. How multiple cues impact interfacial migration has not been adequately addressed.

By studying cell migratory behaviour at the interface of two hydrogel substrates, we identify adhesivity and stiffness as two critical factors that can be tuned to maximize cell migration.

We foresee a potential use of this knowledge in the design of tissue adhesives for wound healing applications.

中文翻译：

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通过粘合各向异性和刚度的整体调整来进行工程界面迁移

界面迁移对于包括形态发生和伤口愈合在内的多个过程至关重要。但是，尚未充分研究界面迁移对界面微环境性质的敏感性。在这里，我们通过在两个水凝胶的界面上跟踪3T3成纤维细胞的运动来解决这个问题。通过将细胞夹在两个粘合剂凝胶（由甲基丙烯酸明胶组成）之间或粘合剂和非粘合剂凝胶（由吉兰糖醇组成）之间，我们发现在后者的情况下，细胞具有更高的运动能力。通过调整结冷胶的整体刚度，我们可以显示出以刚度相关的方式调节了运动性。在最坚硬的凝胶中观察到的最快运动性与细胞高度增加有关，提示刚度介导的细胞骨架组装。收缩激动剂和肌动蛋白解聚药物对细胞运动的抑制是一种迁移方式的指示，其中细胞结合了在其基部施加的收缩牵引力和在顶表面上基于肌动蛋白的推力来推动自身向前发展。在一起，我们的结果表明，背腹粘附各向异性和刚度可以共同调整，以工程界面迁移。

重要声明

越来越多地理解，细胞在体内通过通常在基质中以孔隙形式出现的封闭空间以及存在于相邻ECM纤维之间或基质与脉管系统之间的天然存在的界面在体内迁移。当通过用粘合剂覆盖伤口来治疗皮肤表面上的伤口时，也会产生这样的界面。多个线索如何影响界面迁移尚未得到充分解决。

通过研究两种水凝胶基质的界面上的细胞迁移行为，我们确定了粘附性和刚度是可以调整以最大化细胞迁移的两个关键因素。

我们预见到这种知识在伤口愈合应用的组织粘合剂设计中的潜在用途。