Katarina Wolf
 

Microscopical Imaging of the Cell, Department of Cell Biology, NCMLS, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands

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Cells moving through extracellular matrix (ECM) are confronted with collagen fibrils and bundles which serve as substrate for adhesion, traction and guidance but also form a physical barrier against the advancing cell body. Mechanistically, migrating cells employ two concurrent strategies to overcome physical tissue constraints, such as (i) localized pericellular proteolysis of ECM components leading to opened ECM gaps and realigned trails, and (ii) deformation of cell body and nucleus to navigate through narrow ECM pores. We here define the mechanisms and physical limits of protease-dependent and -independent migration, respectively, using different cell types, together with degradable three-dimensional (3D) fibrillar lattices of different density reconstituted from cross-linked or non-cross-linked type I collagen, and non-degradable polycarbonate transwell filters of different pore size. The data show relative (5 to 3 µm pore diameter) and absolute limits (3 to 1 µm pore diameter) of cell migration in 3D tissue and identify physical thresholds below which the deformation of the nucleus is insufficient to maintain migration. In context, the physical dimensions of ECM gaps and pores, the availability of surface proteases, as well as the nuclear shape and deformability control cell morphology and efficiency in cell migration.