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• W3081165959 endingPage "e1008160" @default.
• W3081165959 startingPage "e1008160" @default.
• W3081165959 abstract "Cell migration through a three-dimensional (3D) extracellular matrix (ECM) underlies important physiological phenomena and is based on a variety of mechanical strategies depending on the cell type and the properties of the ECM. By using computer simulations of the cell's mid-plane, we investigate two such migration mechanisms-'push-pull' (forming a finger-like protrusion, adhering to an ECM node, and pulling the cell body forward) and 'rear-squeezing' (pushing the cell body through the ECM by contracting the cell cortex and ECM at the cell rear). We present a computational model that accounts for both elastic deformation and forces of the ECM, an active cell cortex and nucleus, and for hydrodynamic forces and flow of the extracellular fluid, cytoplasm, and nucleoplasm. We find that relations between three mechanical parameters-the cortex's contractile force, nuclear elasticity, and ECM rigidity-determine the effectiveness of cell migration through the dense ECM. The cell can migrate persistently even if its cortical contraction cannot deform a near-rigid ECM, but then the contraction of the cortex has to be able to sufficiently deform the nucleus. The cell can also migrate even if it fails to deform a stiff nucleus, but then it has to be able to sufficiently deform the ECM. Simulation results show that nuclear stiffness limits the cell migration more than the ECM rigidity. Simulations show the rear-squeezing mechanism of motility results in more robust migration with larger cell displacements than those with the push-pull mechanism over a range of parameter values. Additionally, results show that the rear-squeezing mechanism is aided by hydrodynamics through a pressure gradient." @default.
• W3081165959 created "2020-09-01" @default.
• W3081165959 creator A5061742608 @default.
• W3081165959 creator A5079796040 @default.
• W3081165959 creator A5080045169 @default.
• W3081165959 date "2020-08-27" @default.
• W3081165959 modified "2023-10-14" @default.
• W3081165959 title "Computational estimates of mechanical constraints on cell migration through the extracellular matrix" @default.
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• W3081165959 doi "https://doi.org/10.1371/journal.pcbi.1008160" @default.
• W3081165959 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7480866" @default.
• W3081165959 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32853248" @default.
• W3081165959 hasPublicationYear "2020" @default.
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