Cell aggregation on nanorough surfaces.

The ability to control adhesion and the spatial organization of cells over nanoscale surfaces is essential in tissue engineering, regenerative medicine, the growth of organoids and spheroids as an in-vitro-model of human development and disease. Nonetheless, despite the several different works that have explored the influence of nanotopography on cell adhesion and clustering, little is known about how the forces arising from membrane conformational change developing during cell adaptation to a nanorough surface, and the cell-cell adhesion forces, interact to guide cell assembly. Here, starting from the works of Decuzzi and Ferrari, who examined how the energy of a cell varies while adhering to a nanoscale surface, and of Armstrong and collaborators, who developed a continuous model of cell-cell adhesion and morphogenesis, we provide a description of how nanotopography can modulate cellular clustering. In simulations where the parameters of the model were varied over large intervals, we found that nanoroughness may induce cell aggregation from a homogenous, uniform state, also for weak cell-cell adhesion. Results of the model are relevant in bio-engineering and biomedical nanotechnology, and may be of interest for those involved in the design and fabrication of biomaterials and scaffolds for tissue formation and repair.