Physical role of nuclear and cytoskeletal confinements in cell migration mode selection and switching

Abstract

There exists a large complexity and high plasticity in migration modes dependent on cell type, cell condition such physiological or pathological stages, microenvironmental conditions such as dimensionality, structural architecture, composition and adhesiveness, as well as cellular mechanical and tissue mechanical properties. The current knowledge on the plasticity in migration modes is limited and not yet fully understood. Many descriptions are fully based on biological and biochemical observations or instead focus entirely on biophysical parameters without integrating biological knowledge. Here, the biological approaches are compared with the biophysical approaches to understand and predict migration modes as well as their switching conditions in order to reveal the mechanical properties. The mechanical properties such as the stiffness can regulate the invasiveness and hence subsequently serve as a biomarker for invasiveness. However, the impact of the nuclear deformability on cellular motility and the impact of the cytoskeletal deformability are controversially discussed. In more detail, there are two different opinions: on the one hand it is stated that the nuclear deformability predicts solely cell migration independent of the cytoskeletal deformability and on the other hand it is stated that the cellular deformability regulates the nuclear deformability to facilitate cellular motility. In this review, it is pointed out and discussed what impact the nuclear confinement and the cytoskeletal confinement have on the selection of the individual migration mode and on how a switch between the migration modes is performed. Moreover, it is discussed whether the nuclear confinement is regulated by the cytoskeletal confinement such as an apical actin filament based capping structure over the entire nucleus. Finally, mechanical parameters such as the nuclear or cytoskeletal deformability may serve as a biomarker for cell migration and invasion in healthy, physiological and pathological processes such as cancer.