RT Journal Article
SR Electronic
T1 A novel model of multicellular communication through extracellular matrix microstructure
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.21.514608
DO 10.1101/2022.11.21.514608
A1 John Metzcar
A1 Ben S. Duggan
A1 Brandon Fischer
A1 Matthew Murphy
A1 Paul Macklin
YR 2022
UL http://biorxiv.org/content/early/2022/11/22/2022.11.21.514608.abstract
AB Extracellular matrix (ECM) is a key part of the cellular microenvironment and critical in multiple disease and developmental processes. Representing ECM and cell-ECM interactions is a challenging multi-scale problem that acts across the tissue and cell scales. While several computational frameworks exist for ECM modeling, they typically focus on very detailed modeling of individual ECM fibers or represent only a single aspect of the ECM. Using the PhysiCell agent-based modeling platform, we combine aspects of previous modeling efforts and develop a framework of intermediate detail that addresses direct cell-ECM interactions. We represent a small region of ECM as an ECM element containing 3 variables: anisotropy, density, and orientation. We then place many ECM elements through a space to form an ECM. Cells have a mechanical response to the local ECM variables and remodel ECM based on their velocity. We demonstrate aspects of this framework with a model of cell invasion where the cell’s motile phenotype is driven by the ECM microstructure patterned by prior cells’ movements. Investigating the limit of high-speed communication and with stepwise introduction of the framework features, we generate a range of cellular dynamics and ECM patterns – from recapitulating a homeostatic tissue, to indirect communication of paths (stigmergy), to collective migration. When we relax the high-speed communication assumption, we find that the behaviors persist but can be lost as rate of signal generation declines. This result suggests that cell-cell communication mitigated via the ECM can constitute an important mechanism for pattern formation in dynamic cellular patterning while other processes likely also contribute to leader-follower behavior.Competing Interest StatementThe authors have declared no competing interest.