Cells can migrate through tight spaces by adopting an amoeboid-like motility, characterized by blebbing and minimal proteolytic degradation of the surrounding extracellular matrix (ECM). Driscoll et al. report that amoeboid-like migration can create ECM tunnels by a process they term ‘worrying’, in which large blebs abrade collagen.

The authors used melanoma cells, known for amoeboid migration, and found that they form rounded cells with small transient blebs when transplanted into zebrafish. Melanoma cells in 3D collagen in vitro adopted either faster-moving extended mesenchymal, or slower-moving rounded, morphologies, with the latter associated with more metastatic melanomas. The amoeboid cells formed tunnels through collagen even with protease inhibitors, which suggests that tunnelling is independent of proteolysis. Instead, repeated bleb protrusion and retraction slowly fragment collagen and internalize collagen fragments. The authors found that polarized bleb formation is downstream of PI3K and ARP2/3-mediated actin polymerization.

细胞可以通过采用类似变形虫的运动在狭小空间内迁移，其特征是周围细胞外基质 （ECM） 的起泡和最小的蛋白水解降解。Driscoll 等人报告说，阿米巴样迁移可以通过他们称之为 “令人担忧 ”的过程产生 ECM 隧道，其中大水泡会磨损胶原蛋白。

作者使用了以变形虫迁移而闻名的黑色素瘤细胞，发现当移植到斑马鱼中时，它们会形成带有小瞬时气泡的圆形细胞。体外 3D 胶原蛋白中的黑色素瘤细胞采用移动较快的扩展间充质或移动较慢的圆形形态，后者与更多的转移性黑色素瘤相关。即使使用蛋白酶抑制剂，变形虫细胞也会通过胶原蛋白形成隧道，这表明隧道形成独立于蛋白水解。相反，重复的气泡突出和回缩会缓慢地使胶原蛋白碎裂并内化胶原蛋白碎片。作者发现极化气泡形成位于 PI3K 和 ARP2/3 介导的肌动蛋白聚合的下游。