Tissue-Intrinsic Shape Mechanics in Growing Pre-Migratory Tumor Spheroids

One of the hallmarks of pre-migratory tumors is the progressive loss of compact morphology. To investigate how tumors may intrinsically regulate their shape during growth, we employ a three-dimensional (3D) vertex model of multicellular aggregates that incorporates key structural features of tumor spheroids, including its surface, a proliferative rim, and a necrotic core. Focusing exclusively on tumor-intrinsic mechanical interactions, we examine how their collective effects guide morphological evolution en route to metastasis. We show that spheroids acquire lobulated morphologies through an interplay between differential tensions at the spheroid surface and the living-necrotic interface (LNI), together with differential growth within the proliferative rim. In addition, spheroid shapes can be substantially modulated by tissue rheological properties emerging from active, cell-scale forces. Our cell- and tissue-scale simulations of tumor morphologies are enabled by a computational framework that overcomes a major limitation of 3D vertex models - the lack of cell-division - by introducing a graph-based polyhedral-division algorithm within the Graph Vertex Model (GVM).