Mechanisms of 3D cell migration

We search in this paper for context-specific modes of three-dimensional (3D) cell migration using imaging for phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and active Rac1 and Cdc42 in primary fibroblasts migrating within different 3D environments. In 3D collagen, PIP3 and active Rac1 and Cdc42 were targeted to the leading edge, consistent with lamellipodia-based migration. In contrast, elongated cells migrating inside dermal explants and the cell-derived matrix (CDM) formed blunt, cylindrical protrusions, termed lobopodia, and Rac1, Cdc42, and PIP3 signaling was nonpolarized. Reducing RhoA, Rho-associated protein kinase (ROCK), or myosin II activity switched the cells to lamellipodia-based 3D migration. These modes of 3D migration were regulated by matrix physical properties. Specifically, experimentally modifying the elasticity of the CDM or collagen gels established that nonlinear elasticity supported lamellipodia-based migration, whereas linear elasticity switched cells to lobopodia-based migration. Thus, the relative polarization of intracellular signaling identifies two distinct modes of 3D cell migration governed intrinsically by RhoA, ROCK, and myosin II and extrinsically by the elastic behavior of the 3D extracellular matrix.

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Controlled architectural and chemotactic studies of 3D cell migration

Biomaterials ◽

10.1016/j.biomaterials.2010.12.019 ◽

2011 ◽

Vol 32 (10) ◽

pp. 2634-2641 ◽

Cited By ~ 39

Author(s):

Prakriti Tayalia ◽

Eric Mazur ◽

David J. Mooney

Keyword(s):

Cell Migration ◽

3D Cell Migration

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One-dimensional topography underlies three-dimensional fibrillar cell migration

The Journal of Cell Biology ◽

10.1083/jcb.200810041 ◽

2009 ◽

Vol 184 (4) ◽

pp. 481-490 ◽

Cited By ~ 515

Author(s):

Andrew D. Doyle ◽

Francis W. Wang ◽

Kazue Matsumoto ◽

Kenneth M. Yamada

Keyword(s):

Cell Culture ◽

Extracellular Matrix ◽

Cell Migration ◽

Myosin Ii ◽

Three Dimensional ◽

Two Dimensional ◽

Ligand Density ◽

One Dimensional ◽

3D Cell Migration ◽

Striking Contrast

Current concepts of cell migration were established in regular two-dimensional (2D) cell culture, but the roles of topography are poorly understood for cells migrating in an oriented 3D fibrillar extracellular matrix (ECM). We use a novel micropatterning technique termed microphotopatterning (μPP) to identify functions for 1D fibrillar patterns in 3D cell migration. In striking contrast to 2D, cell migration in both 1D and 3D is rapid, uniaxial, independent of ECM ligand density, and dependent on myosin II contractility and microtubules (MTs). 1D and 3D migration are also characterized by an anterior MT bundle with a posterior centrosome. We propose that cells migrate rapidly through 3D fibrillar matrices by a 1D migratory mechanism not mimicked by 2D matrices.

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Mechanotransduction of fluid stresses governs 3D cell migration

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1316848111 ◽

2014 ◽

Vol 111 (7) ◽

pp. 2447-2452 ◽

Cited By ~ 138

Author(s):

W. J. Polacheck ◽

A. E. German ◽

A. Mammoto ◽

D. E. Ingber ◽

R. D. Kamm

Keyword(s):

Cell Migration ◽

3D Cell Migration

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Computational estimates of mechanical constraints on cell migration through the extracellular matrix

10.1101/2020.01.19.912006 ◽

2020 ◽

Author(s):

Ondrej Maxian ◽

Alex Mogilner ◽

Wanda Strychalski

Keyword(s):

Extracellular Matrix ◽

Cell Migration ◽

Pressure Gradient ◽

Cell Body ◽

Fluid Pressure ◽

Three Dimensional ◽

Extracellular Fluid ◽

Cell Cortex ◽

3D Cell Migration ◽

Parameter Values

AbstractCell 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, 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 of 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.Author summaryComputational simulations of models representing two different mechanisms of 3D cell migration in an extracellular matrix are presented. One mechanism represents a mesenchymal mode, characterized by finger-like actin protrusions, while the second mode is more amoeboid in that rear contraction of the cortex propels the cell forward. In both mechanisms, the cell generates a thin actin protrusion on the cortex that attaches to an ECM node. The cell is then either pulled (mesenchymal) or pushed (amoeboid) forward. Results show both mechanisms result in successful migration over a range of simulated parameter values as long as the contractile tension of the cortex exceeds either the nuclear stiffness or ECM stiffness, but not necessarily both. However, the distance traveled by the amoeboid migration mode is more robust to changes in parameter values, and is larger than in simulations of the mesenchymal mode. Additionally cells experience a favorable fluid pressure gradient when migrating in the amoeboid mode, and an adverse fluid pressure gradient in the mesenchymal mode.

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