Pore Shape Defines Paths of Metastatic Cell Migration

Nano Letters
Brenda J GreenAldo Ferrari

Abstract

Invasion of dense tissues by cancer cells involves the interplay between the penetration resistance offered by interstitial pores and the deformability of cells. Metastatic cancer cells find optimal paths of minimal resistance through an adaptive path-finding process, which leads to successful dissemination. The physical limit of nuclear deformation is related to the minimal cross section of pores that can be successfully penetrated. However, this single biophysical parameter does not fully describe the architectural complexity of tissues featuring pores of variable area and shape. Here, employing laser nanolithography, we fabricate pore microenvironment models with well-controlled pore shapes, through which human breast cells (MCF10A) and their metastatic offspring (MCF10CA1a.cl1) could pervade. In these experimental settings, we demonstrate that the actual pore shape, and not only the cross section, is a major and independent determinant of cancer penetration efficiency. In complex architectures containing pores demanding large deformations from invading cells, tall and narrow rectangular openings facilitate cancer migration. In addition, we highlight the characteristic traits of the explorative behavior enabling metastatic c...Continue Reading

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Citations

Aug 17, 2018·Molecular Biology of the Cell·Magdalini PanagiotakopoulouAldo Ferrari
Aug 21, 2019·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Viola SgarminatoGianluca Ciardelli

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