Deformability and collision-induced reorientation enhance cell topotaxis in dense microenvironments

Leonie van Steijn*, Joeri Wondergem, Koen Schakenraad, Doris Heinrich, Roeland Merks

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

In vivo, cells navigate through complex environments filled with obstacles such as other cells and the extracellular matrix. Recently, the term “topotaxis” has been introduced for navigation along topographic cues such as obstacle density gradients. Experimental and mathematical efforts have analyzed topotaxis of single cells in pillared grids with pillar density gradients. A previous model based on active Brownian particles (ABPs) has shown that ABPs perform topotaxis, i.e., drift toward lower pillar densities, due to decreased effective persistence lengths at high pillar densities. The ABP model predicted topotactic drifts of up to 1% of the instantaneous speed, whereas drifts of up to 5% have been observed experimentally. We hypothesized that the discrepancy between the ABP and the experimental observations could be in 1) cell deformability and 2) more complex cell-pillar interactions. Here, we introduce a more detailed model of topotaxis based on the cellular Potts model (CPM). To model persistent cells we use the Act model, which mimics actin-polymerization-driven motility, and a hybrid CPM-ABP model. Model parameters were fitted to simulate the experimentally found motion of Dictyostelium discoideum on a flat surface. For starved D. discoideum, the topotactic drifts predicted by both CPM variants are closer to the experimental results than the previous ABP model due to a larger decrease in persistence length. Furthermore, the Act model outperformed the hybrid model in terms of topotactic efficiency, as it shows a larger reduction in effective persistence time in dense pillar grids. Also pillar adhesion can slow down cells and decrease topotaxis. For slow and less-persistent vegetative D. discoideum cells, both CPMs predicted a similar small topotactic drift. We conclude that deformable cell volume results in higher topotactic drift compared with ABPs, and that feedback of cell-pillar collisions on cell persistence increases drift only in highly persistent cells.
Original languageEnglish
Pages (from-to)2791-2807
Number of pages17
JournalBiophysical Journal
Volume122
Issue number13
DOIs
Publication statusPublished - 11 Jul 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 Biophysical Society

Funding

We thank SURFsara for the support and computing time in using the Lisa cluster computer. J.A.J.W. and D.H. acknowledge the Fraunhofer Society for the Fraunhofer Attract grant “3DNanoCell” for partly funding this work and thank Dr. Günther Gerisch (Max Planck Institute of Biochemistry, Martinsried, Germany) for providing axenic D. discoideum (Ax2) with both free GFP and limGFP in lim0 insertion. R.M.H.M. was funded by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek grant NWO/ENW-VICI 865.17.004 .

FundersFunder number
Fraunhofer Society for the Fraunhofer Attract
Max Planck Institute of Biochemistry
Nederlandse Organisatie voor Wetenschappelijk OnderzoekNWO/ENW-VICI 865.17.004

    Keywords

    • Dictyostelium
    • Extracellular Matrix
    • Motion

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