Designing Optimal Scaffold Topographies to Promote Nucleus-Guided Mechanosensitive Cell Migration Using in Silico Models

Abstract

Computational models have become an essential part of exploratory protocols in cell biology, as a complement to in vivo or in vitro experiments. These virtual models have the twofold advantage of enabling access to new types of data and validate complex theories. The design of mechanically functionalized biomaterials or scaffolds, to promote cell proliferation and invasion in the absence or in the complement of synthetic chemical coatings, can certainly benefit from these hybrid testing approaches. The underlying fundamental process of cell migration and in particular its dependence on the cell mechanical/geometrical environment remains crudely understood. Currently at least two theories explain the migration patterns observed by cells on curved topographies, involving either polymerization dynamics of actin or assembly dynamics of focal adhesions. We recently proposed a third mechanism relying on nucleus mechanosensitivity, which has been tested extensively experimentally and computationally. We now explore the hypothesis that nucleosensitivity could be a mechanism for cells to optimally find microenvironments suited for mitosis, providing mechanical stability and relaxation. By means of a computational mechanical model with intracellular structure detail, we investigate how the complex interplay between this new migration mechanism and the microenvironment topography can lead to more relaxed cells and organelles. To go further, we simulated in this study cell migration via a novel protocol in silico which generates dynamical ripple wave on a deformable substrate and changes topography over time. This kind of in silico protocols based on a new understanding of cell migration and nucleosensitivity could, therefore, inform the design of optimized scaffold topographies for cell invasion and proliferation.