Principles of cellular behavior: integrating cellular structure, dynamics, and decision making in a unicellular walker

Although it may be easy to think of cells as little more than the simple building blocks of more complex organisms, single cells are capable of remarkably sophisticated behaviors. Such behaviors, necessary for survival of microbes in the diverse environments they inhabit as well as for the proper function and development of our own bodies, emerge from the interactions among myriad molecular components in conjunction with physical constraints and mechanisms that dictate interactions between the cell and its environment. We seek to navigate this mechanistic complexity using Euplotes, a ciliate that walks across surfaces using motile appendages (cirri) composed of bundles of cilia, as a model system. Drawing on ideas from non-equilibrium physics and computer science, we demonstrate finite state machine-like processing embodied in walking Euplotes eurystomus cells. We found that cellular walking entails regulated transitions between a discrete set of gait states. The set of observed transitions decomposes into a small group of high-probability, temporally irreversible transitions and a large group of low-probability time-symmetric transitions, thus revealing stereotypy in sequential patterns of state transitions. Simulations and experiments suggest that the sequential logic of the gait is functionally important. Taken together, these findings implicate a finite state machine-like process. Cirri are connected by microtubule bundles (fibers), and we found that the dynamics of cirri involved in different state transitions are associated with the structure of the fiber system. Perturbative experiments revealed that the fibers mediate gait coordination, suggesting a mechanical basis of gait control. Ultimately, we aim to elucidate general principles of the regulation and evolution of cellular behavior by integrating understanding across scales of biological organization, linking cellular structure and physiology to patterns of behavior to environmental contexts.