Title: The morphodynamics of 3D migrating cancer cells,
Abstract: Cell shape is an important biomarker. Previously extensive studies have
established the relation between cell shape and cell function. However, the
morphodynamics, namely the temporal fluctuation of cell shape is much less
understood. We study the morphodynamics of MDA-MB-231 cells in type I collagen
extracellular matrix (ECM). We find ECM mechanics, as tuned by collagen
concentration, controls the morphodynamics but not the static cell morphology.
By employing machine learning techniques, we classify cell shape into five
different morphological phenotypes corresponding to different migration modes.
As a result, cell morphodynamics is mapped into temporal evolution of
morphological phenotypes. We systematically characterize the phenotype dynamics
including occurrence probability, dwell time, transition flux, and also obtain
the invasion characteristics of each phenotype. Using a tumor organoid model,
we show that the distinct invasion potentials of each phenotype modulate the
phenotype homeostasis. Overall invasion of a tumor organoid is facilitated by
individual cells searching for and committing to phenotypes of higher invasive
potential. In conclusion, we show that 3D migrating cancer cells exhibit rich
morphodynamics that is regulated by ECM mechanics and is closely related with
cell motility. Our results pave the way to systematic characterization and
functional understanding of cell morphodynamics.