Local actin dynamics couple speed and persistence in a cellular Potts model of cell migration

Wortel, Inge M N; Niculescu, Ioana; Kolijn, P. Martijn; Gov, Nir S.; Boer, Rob J. de; Textor, Johannes

doi:10.1016/j.bpj.2021.04.036

Cited by 37 publications

(39 citation statements)

References 68 publications

(111 reference statements)

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“…In other words, the polarization vector was not directly born out from the cell shape. We should indicate that there are variants of the CPM where polarization and persistence emerge from the underling actin dynamics [ 47 , 48 ], and therefore motility and persistence are highly shape dependent. Currently, it is not clear how critical to have the polarization vector evaluated from the cell shape directly.…”

Section: Discussionmentioning

confidence: 99%

Neighbor-enhanced diffusivity in dense, cohesive cell populations

Lee

2021

PLoS Comput Biol

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The dispersal or mixing of cells within cellular tissue is a crucial property for diverse biological processes, ranging from morphogenesis, immune action, to tumor metastasis. With the phenomenon of ‘contact inhibition of locomotion,’ it is puzzling how cells achieve such processes within a densely packed cohesive population. Here we demonstrate that a proper degree of cell-cell adhesiveness can, intriguingly, enhance the super-diffusive nature of individual cells. We systematically characterize the migration trajectories of crawling MDA-MB-231 cell lines, while they are in several different clustering modes, including freely crawling singles, cohesive doublets of two cells, quadruplets, and confluent population on two-dimensional substrate. Following data analysis and computer simulation of a simple cellular Potts model, which faithfully recapitulated all key experimental observations such as enhanced diffusivity as well as periodic rotation of cell-doublets and cell-quadruplets with mixing events, we found that proper combination of active self-propelling force and cell-cell adhesion is sufficient for generating the observed phenomena. Additionally, we found that tuning parameters for these two factors covers a variety of different collective dynamic states.

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Section: Discussionmentioning

confidence: 99%

Neighbor-enhanced diffusivity in dense, cohesive cell populations

Lee

2021

PLoS Comput Biol

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“…B. Beltman, Marée, Lynch, et al, 2007;Szabó et al, 2010), and 2) the Act model, which provides cells with persistence by modeling local actin dynamics (Niculescu, Textor, and Boer, 2015;Wortel, Niculescu, et al, 2021). We explored a wide range of parameter values for both the basic persistence model and the Act model to investigate whether either of these CPM persistence extensions could reproduce the increases in speed and persistence with density observed in the HCC38 cell line.…”

Section: Previous Cellular Potts Migration Models Do Not Explain Observed Hcc38 Speed-density Behaviormentioning

confidence: 99%

“…In the base CPM (see Materials & Methods) cell motion is driven only by adhesion and cell volume requirements, and therefore cells display Brownian motion, i.e. without any preferred direction and/or persistence (Wortel, Niculescu, et al, 2021). To model persistent cell migration realistically several extensions to the CPM have been proposed: 1) the 'basic persistence model' in which membrane extensions that move a cell in the same direction as its target direction (derived from previous moving 9 Beltman, Marée, Lynch, et al, 2007;Szabó et al, 2010), and 2) the Act model, which provides cells with persistence by modeling local actin dynamics (Niculescu, Textor, and Boer, 2015;Wortel, Niculescu, et al, 2021).…”

Section: Previous Cellular Potts Migration Models Do Not Explain Observed Hcc38 Speed-density Behaviormentioning

confidence: 99%

“…without any preferred direction and/or persistence (Wortel, Niculescu, et al, 2021). To model persistent cell migration realistically several extensions to the CPM have been proposed: 1) the 'basic persistence model' in which membrane extensions that move a cell in the same direction as its target direction (derived from previous moving 9 Beltman, Marée, Lynch, et al, 2007;Szabó et al, 2010), and 2) the Act model, which provides cells with persistence by modeling local actin dynamics (Niculescu, Textor, and Boer, 2015;Wortel, Niculescu, et al, 2021). We explored a wide range of parameter values for both the basic persistence model and the Act model to investigate whether either of these CPM persistence extensions could reproduce the increases in speed and persistence with density observed in the HCC38 cell line.…”

Section: Previous Cellular Potts Migration Models Do Not Explain Observed Hcc38 Speed-density Behaviormentioning

confidence: 99%

“…where GM Act (v) is the geometric mean of all activities of lattice sites in the Moore neighborhood of v which share the same cell identifier σ(v) (Niculescu, Textor, and Boer, 2015;Wortel, Niculescu, et al, 2021).…”

Section: Existing Persistence Modelsmentioning

confidence: 99%

See 2 more Smart Citations

Density-dependent migration characteristics of cancer cells driven by pseudopod coordination

Burger

Water²,

Dévédec³

et al. 2021

Preprint

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The ability of cancer cells to invade neighboring tissue from primary tumors is an important determinant of metastatic behavior. Quantification of cell migration characteristics such as migration speed and persistence helps to understand the requirements for such invasiveness. One factor that may influence invasion is how local tumor cell density shapes cell migration characteristics, which we here investigate with a combined experimental and computational modeling approach. First, we generated and analyzed time-lapse imaging data on two aggressive Triple-Negative Breast Cancer (TNBC) cell lines, HCC38 and Hs578T, during 2D migration assays at various cell densities. HCC38 cells exhibited a counter-intuitive increase in speed and persistence with increasing density, whereas Hs578T did not exhibit such an increase. Moreover, HCC38 cells exhibited strong cluster formation with active pseudopod-driven migration, especially at low densities, whereas Hs578T cells maintained a dispersed positioning. In order to obtain a mechanistic understanding of the density-dependent cell migration characteristics and cluster formation, we developed realistic spatial simulations using a Cellular Potts Model (CPM) with an explicit description of pseudopod dynamics. Model analysis demonstrated that strong coordination between pseudopods within single cells could explain the experimentally observed increase in speed and persistence with increasing density in HCC38 cells. Thus, the density-dependent migratory behavior could be an emergent property of single-cell characteristics without the need for additional mechanisms. This implies that coordination amongst pseudopods may play a role in the aggressive nature of cancers through mediating dispersal.

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Cell Shape and Forces in Elastic and Structured Environments: From Single Cells to Organoids

Link

Weißenbruch

Tanaka

et al. 2023

Adv Funct Materials

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With the advent of mechanobiology, cell shape and forces have emerged as essential elements of cell behavior and fate, in addition to biochemical factors such as growth factors. Cell shape and forces are intrinsically linked to the physical properties of the environment. Extracellular stiffness guides migration of single cells and collectives as well as differentiation and developmental processes. In confined environments, cell division patterns are altered, cell death or extrusion might be initiated, and other modes of cell migration become possible. Tools from materials science such as adhesive micropatterning of soft elastic substrates or direct laser writing of 3D scaffolds have been established to control and quantify cell shape and forces in structured environments. Herein, a review is given on recent experimental and modeling advances in this field, which currently moves from single cells to cell collectives and tissue. A very exciting avenue is the combination of organoids with structured environments, because this will allow one to achieve organotypic function in a controlled setting well suited for long‐term and high‐throughput culture.

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Local actin dynamics couple speed and persistence in a cellular Potts model of cell migration

Cited by 37 publications

References 68 publications

Neighbor-enhanced diffusivity in dense, cohesive cell populations

Neighbor-enhanced diffusivity in dense, cohesive cell populations

Density-dependent migration characteristics of cancer cells driven by pseudopod coordination

Cell Shape and Forces in Elastic and Structured Environments: From Single Cells to Organoids

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