Revach Or-Yam, Weiner Allon, Rechav Katya, Sabanay Ilana, Livne Ariel, Geiger Benjamin
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot 7610001, Israel.
Sci Rep. 2015 Mar 30;5:9466. doi: 10.1038/srep09466.
Invadopodia are actin-rich membrane protrusions through which cells adhere to the extracellular matrix and degrade it. In this study, we explored the mechanical interactions of invadopodia in melanoma cells, using a combination of correlative light and electron microscopy. We show here that the core actin bundle of most invadopodia interacts with integrin-containing matrix adhesions at its basal end, extends through a microtubule-rich cytoplasm, and at its apical end, interacts with the nuclear envelope and indents it. Abolishment of invadopodia by microtubules or src inhibitors leads to the disappearance of these nuclear indentations. Based on the indentation profile and the viscoelastic properties of the nucleus, the force applied by invadopodia is estimated to be in the nanoNewton range. We further show that knockdown of the LINC complex components nesprin 2 or SUN1 leads to a substantial increase in the prominence of the adhesion domains at the opposite end of the invadopodia. We discuss this unexpected, long-range mechanical interplay between the apical and basal domains of invadopodia, and its possible involvement in the penetration of invadopodia into the matrix.
侵袭伪足是富含肌动蛋白的膜突出物，细胞通过它附着于细胞外基质并对其进行降解。在本研究中，我们结合相关光学显微镜和电子显微镜技术，探索了黑色素瘤细胞中侵袭伪足的力学相互作用。我们在此表明，大多数侵袭伪足的核心肌动蛋白束在其基部末端与含整合素的基质黏附相互作用，穿过富含微管的细胞质延伸，在其顶端与核膜相互作用并使其凹陷。微管或src抑制剂消除侵袭伪足会导致这些核凹陷消失。根据核的凹陷轮廓和粘弹性特性，侵袭伪足施加的力估计在纳牛顿范围内。我们进一步表明，LINC复合物成分nesprin 2或SUN1的敲低会导致侵袭伪足另一端黏附结构域的突出显著增加。我们讨论了侵袭伪足顶端和基部结构域之间这种意想不到的远程力学相互作用，以及它可能在侵袭伪足穿透基质中的作用。
