Reciprocal intra- and extra-cellular polarity enables deep mechanosensing through layered matrices.
Reciprocal intra- and extra-cellular polarity enables deep mechanosensing through layered matrices.
复制标题
细胞内和细胞外的相互极性使得能够通过分层矩阵进行深度机械传感。
DOI：
10.1016/j.celrep.2023.112362
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发表时间：
2023
期刊：
影响因子：
8.8
通讯作者：
Pathak,Amit
中科院分区：
文献类型：
--
作者：
Walter,Christopher;Mathur,Jairaj;Pathak,Amit
贴壁细胞在层状组织界面上迁移，驱动形态发生、伤口愈合和肿瘤侵袭。虽然已知较硬的表面可以增强细胞迁移，但细胞是否能感知埋在较软纤维基质下的基底坚硬环境仍不清楚。使用层状胶原-聚丙烯酰胺凝胶系统，我们揭示了由细胞-基质极性驱动的迁移表型。此处，基底基质坚硬的癌细胞（而非正常细胞）产生稳定的突起，迁移速度更快，胶原蛋白变形更大，因为通过顶部胶原蛋白层的“深度机械感应”。前后极性的癌细胞突起使极化的胶原硬化变形。通过胶原交联、激光消融或Arp2/3抑制来破坏细胞外或细胞内极性，可以独立地消除癌细胞的深度机械敏感性迁移。我们的实验发现，通过基于晶格的能量最小化模型验证，提出了一种细胞迁移机制，其中极化的细胞突起和收缩性与细胞外的机械极性相互作用，最终形成细胞类型依赖的通过基质层进行机械感知的能力。
Adherent cells migrate on layered tissue interfaces to drive morphogenesis, wound healing, and tumor invasion. Although stiffer surfaces are known to enhance cell migration, it remains unclear whether cells sense basal stiff environments buried under softer, fibrous matrix. Using layered collagen-polyacrylamide gel systems, we unveil a migration phenotype driven by cell-matrix polarity. Here, cancer (but not normal) cells with stiff base matrix generate stable protrusions, faster migration, and greater collagen deformation because of "depth mechanosensing" through the top collagen layer. Cancer cell protrusions with front-rear polarity produce polarized collagen stiffening and deformations. Disruption of either extracellular or intracellular polarity via collagen crosslinking, laser ablation, or Arp2/3 inhibition independently abrogates depth-mechanosensitive migration of cancer cells. Our experimental findings, validated by lattice-based energy minimization modeling, present a cell migration mechanism whereby polarized cellular protrusions and contractility are reciprocated by mechanical extracellular polarity, culminating in a cell-type-dependent ability to mechanosense through matrix layers.