A General Scaling Law Governing Chemotactic and Non-Directed Eukaryotic Cell Motility

Cell motility is a fundamental process with relevance to embryonic development, immune response, and metastasis. Cells move either spontaneously, in a non-directed fashion, or in response to chemotactic signals, in a directed fashion. Even though they are often studied separately, both forms of motility share many complex processes at the molecular and subcellular scale, e.g., orchestrated cytoskeletal rearrangements and polarization. In addition, at the cellular level both types of motility include persistent runs interspersed with reorientation pauses. Because there is a great range of variability in motility among different cell types, a key challenge in the field is to integrate these multi-scale processes into a coherent framework. We analyzed the motility of individual Dictyostelium cells with bimodal analysis, a method that compares time spent in persistent versus reorientation mode. Unexpectedly, we found that reorientation time is coupled with persistent time in an inverse correlation, i.e., if one increases, the other must decrease. Surprisingly, the inverse correlation holds for both non-directed and chemotactic motility, so that the full range of Dictyostelium motility can be described by a single scaling relationship. Additionally, we found an identical scaling relationship for three human cell lines, indicating that the coupling of reorientation and persistence holds across species and making it possible to describe the complexity of cell motility in a surprisingly general and simple manner. Armed with this new perspective, we analyzed the motility of Dictyostelium mutants, and found four in which the coupling between reorientation and persistent modes was altered. Our results point to a fundamental underlying principle, described by a simple scaling law, unifying mechanisms of eukaryotic cell motility at several scales.