Actin-inspired feedback couples speed and persistence in a Cellular Potts Model of cell migration

Abstract

8 9T cells are key effector cells in the immune system that are well-known for their ability to adapt their shape and 10 behavior to environmental cues. It has been suggested that these highly diverse, context-dependent migration 11 patterns reflect an optimization process -where T cells adjust motility parameters such as speed and persistence 12 to aid their search for antigen. Whereas models investigating such "search strategies" typically treat speed and 13 persistence as independent variables, one aspect of cell motility was recently found to be conserved across 14 a large variety of cell types: fast-moving cells turn less frequently. This raises the question whether T cells 15 can tune speed and persistence independently of each other. We therefore investigated to what extent this 16 universal coupling between cell speed and persistence (UCSP) shapes the behavior of migrating T cells. We 17 first show that the UCSP emerges spontaneously in an in silico Cellular Potts Model (CPM) of T cell migration. 18 Our model shows a link between the UCSP and cell shape dynamics, which put an upper bound on both the 19 speed and the persistence a cell can reach. We then use the CPM to examine how environmental constraints 20 affect motility patterns of T cells migrating in the crowded environments they also face in vivo, and show that T 21 cells completely lose their speed-persistence coupling when confined in a densely packed environment such 22 as the epidermis. Thus, although our model further highlights the validity of the UCSP in migrating cells, it 23 also demonstrates that environmental factors may overrule this coupling. Our data show that T cell motility 24 parameters are subject to both cell-intrinsic and extrinsic constraints, suggesting that "optimal" T cell search 25 strategies may not always be attainable in vivo. 26 1 28 T cells have the rare ability to migrate in nearly all tissues within the human body. Especially in tissues with a 29 high risk of infection -like the lung, the gut, and the skin -T cells are continuously on the move in search of 30 foreign invaders. Furthermore, migration in lymphoid organs such as the thymus and lymph nodes is crucial 31 for T cell function. 32Although T cells preserve their motility in these different contexts, they do adapt their morphology and 33 migratory behavior to environmental cues. It has been suggested that this remarkably flexible behavior reflects 34 different "search strategies" that allow T cells to maximize the chance of encountering antigen (Krummel et al., 35 2016). For example, naive T cells rapidly crawl along a network of stromal cells in the lymph node, alternating 36 between short intervals of persistent movement and random changes in direction (Miller et al., 2002(Miller et al., , 2003 37 Bajnoff et al., 2006; Beauchemin et al., 2007). This "stop and go" behavior allows them to cover large areas of the 38 lymph node in a short amount of time, and appears to be a good strategy for finding rare antigens without prior 39 information o...

L‐lactate promotes intestinal epithelial cell migration to inhibit colitis

“…Cell migration is fundamental to establishing and maintaining the homeostasis of tissues 24 . The coupling of cell speed and persistence has been considered as the fundamental property in cell migration 25 . To investigate whether L‐lactate promotes epithelial cell migration through enhancing cell speed and/or persistence, we treated Mode‐K cells with or without L‐lactate and recorded the cell movement every 15 minutes for 24 hours by using a video microscopy (Video S1).…”

Artistoo, a library to build, share, and explore simulations of cells and tissues in the web browser

“…We here show that the framework’s performance (similar to that of existing frameworks in C++) is sufficient to allow for interactive CPM simulations. We have been developing the library for more than 5 years, also using it for robust simulation work in our research; see, for example, Wortel et al, 2020 . We are continuing to develop the library for our own work and welcome suggestions and code contributions from the community.…”

Computational modelling of cell motility modes emerging from cell-matrix adhesion dynamics

“…An experimental study showed this correlation to be a universal coupling between cell speed and cell persistence (UCSP), mediated by actin flow [44], as actin flow stabilizes cell polarity. In our model, the actin flow is modelled phenomenologically by the Act model [19], which displays this UCSP as well [20]. So the observation that B lymphocytes can display slow persistent motility on fibronectin, and much faster Brownian cell motility seems to disagree with UCSP.…”

“…Our computational model is based on the Act model [19,20], an extension of the Cellular Potts model (CPM, [21,22]) for efficient modelling of persistent, amoeboid cell motility emerging from feedback mechanism inspired by detailed insights into actin-polymerization driven cell motility. Depending on its parameter settings, the model produces a variety of realistic cell shapes, cell polarization, and cell trajectories.…”

“…Interestingly, this model can already display multiple motility modes: Simulated cells show intermittent (stop-and-go) or persistent random walks. An in-depth characterization revealed that the model displays universal coupling between speed and persistence, and specifically that speed increases linearly with protrusion strength, whereas persistence time increase exponentially with protrusion strength [20].…”