Constructing Contractile Ensembles: How Cells Build Units of Force Generation

Abstract

Force generation at the cellular level is critical for eukaryotic development, homeostasis, and the progression of force dependent diseases such as cancer. Molecular motors coordinate with cytoskeletal elements, such as actin filaments, to drive force dependent processes such as cell migration, cell division, and muscle contraction. These seemingly diverse processes are all driven by forces generated by the same contractile machinery: actin and myosin II. Despite centuries of research into how cells and tissues generate the forces required for life, how cells build the contractile machinery powering diverse cellular functions is poorly understood. Here, we use two seemingly different experimental systems to study how diverse cell types assemble contractile ensembles. First, we use crawling and dividing cells to demonstrate how cancer cells build contractile ensembles. Using experimental paradigms established in this work, we then use human iPSC-derived cardiac myocytes to demonstrate how heart cells responsible for the beating of the heart assemble their own (related) contractile ensembles.