Biophysical Design Space for Cellular Self-assembly and Dynamics

Abstract

In natural biological systems, cells organize into tissues through interactions of several processes, including cellular signaling, collective migration, contractile activity of cytoskeletal elements and interactions with their surroundings. In recent decades, advancements in microscopy, genetic engineering, biochemistry, and computational modeling have enabled a more quantitative understanding of these processes. In this article, we present an integrated computational framework that couples various physical mechanisms such as cell-cell adhesion, strength and persistence of cellular motility, and the background stiffness. We use this framework to study how they collectively interact to determine the self-organization of the cells from a pseudo-random structure as well as the migration behavior of the cells. Notably, our simulations predict that motility has a two-way effect on cellular self-assembly: it promotes aggregation at moderate levels but disrupts clusters when excessively strong, yielding an optimal motility for formation of multicellular clusters. On the other hand, adhesion shows a two-stage effect: At lower value it self-assembles the structure, at higher value it compacts it. Furthermore, we experimentally demonstrate the motility-assisted self-aggregation of cells using cancer cells in a granular mechanical milieu. Finally we show that cell-cell adhesion and background medium tune the strength and persistence of cellular migration. Altogether, this work presents a computational framework that allows us to design phase behavior of collective of cells tuning their interaction, motility, and the background mechanics.