Department of Chemistry and Center for NanoScience, Ludwig-Maximilians-Universität München, Munich, Germany.
Department of Pharmacy, Ludwig-Maximilians-Universität München, Munich, Germany.
PLoS One. 2019 Nov 13;14(11):e0225215. doi: 10.1371/journal.pone.0225215. eCollection 2019.
Cancer cell migration is influenced by cellular phenotype and behavior as well as by the mechanical and chemical properties of the environment. Furthermore, many cancer cells show plasticity of their phenotype and adapt it to the properties of the environment. Here, we study the influence of fiber stiffness, confinement, and adhesion properties on cancer cell migration in porous collagen gels. Collagen gels with soft fibers abrogate migration and promote a round, non-invasive phenotype. Stiffer collagen fibers are inherently more adhesive and lead to the existence of an adhesive phenotype and in general confined migration due to adhesion. Addition of TGF-β lowers adhesion, eliminates the adhesive phenotype and increases the amount of highly motile amoeboid phenotypes. Highest migration speeds and longest displacements are achieved in stiff collagen fibers in pores of about cell size by amoeboid phenotypes. This elucidates the influence of the mechanical properties of collagen gels on phenotype and subsequently migration and shows that stiff fibers, cell sized pores, and low adhesion, are optimal conditions for an amoeboid phenotype and efficient migration.
癌细胞的迁移受到细胞表型和行为以及环境的力学和化学性质的影响。此外，许多癌细胞表现出其表型的可塑性，并使其适应环境的特性。在这里，我们研究纤维硬度、约束和粘附特性对多孔胶原凝胶中癌细胞迁移的影响。具有柔软纤维的胶原凝胶会阻止迁移并促进圆形、非侵袭性的表型。较硬的胶原纤维本身具有更强的粘附性，并导致存在粘附表型，并且由于粘附通常会限制迁移。添加 TGF-β 会降低粘附性，消除粘附表型，并增加高度迁移的阿米巴样表型的数量。通过阿米巴样表型在大约细胞大小的孔中的硬胶原纤维中实现最高的迁移速度和最长的位移。这阐明了胶原凝胶的力学性质对表型以及随后的迁移的影响，并表明硬纤维、细胞大小的孔和低粘附性是阿米巴样表型和有效迁移的最佳条件。
