Trends in Cell Biology
ReviewFibroblasts Lead the Way: A Unified View of 3D Cell Motility
Section snippets
Moving from 2D to 3D Environments
The ability of cells to navigate diverse 3D environments is essential for many aspects of multicellular life. For example, immune cells patrol structurally diverse tissues to detect and fight infections, while fibroblasts move through the dermis to sites of tissue damage, where they remake the matrix and help to restore the barrier function of the skin. Conversely, the inappropriate 3D migration of metastatic cancer cells can be lethal. Discovering the molecular mechanisms driving 3D fibroblast
The Physical Challenges and Advantages of Moving in a 3D Matrix
Unlike a 2D matrix, a 3D matrix can facilitate the movement of nonadhesive cells [22]. For example, while stationary nonadherent cancer cells form membrane blebs on a 2D surface, they become motile when compressed between two surfaces [23]. This phenomenon can be recapitulated by compressing water droplets containing microtubules, kinesin, and ATP [24], which allows the friction between the flowing microtubules and the confining surfaces to propel the droplet forward. The compression-dependent
The Plasticity of 3D Fibroblast Migration
Nineteenth-century cell biologists recognized that single-cell protists move using a variety of structurally distinct protrusions [51]. These distinct protrusions were first characterized based on morphology. The giant amoeba, Amoeba proteus, uses actomyosin contractility to drive cytoplasmic streaming to increase intracellular pressure and form blunt, cylindrical protrusions termed ‘lobopodia’ [52]. By contrast, low-pressure protists, such as Vanella miroides, crawling on 2D surfaces use actin
Concluding Remarks
The diversity in the mechanisms used by primary fibroblasts to migrate in physiological 3D environments shows there is still much to discover in terms of the molecular mechanisms of cell movement. Given that cells in 3D can use more than one mechanism to migrate, the precise number of these alternative modes of migration and their mechanistic interrelationships needs characterization [65]. Establishing the rules that dictate how cells migrate could narrow down the number of possible mechanisms,
Acknowledgments
We thank C. Parent, A. Doyle, W. Daley, and M. Hague for their critical comments and suggestions on the manuscript. Work in the authors’ laboratory is supported by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research (NIH, NIDCR).
References (69)
The locomotion of fibroblasts in culture. I. Movements of the leading edge
Exp. Cell Res.
(1970)- et al.
Cell migration: a physically integrated molecular process
Cell
(1996) Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells
Cell
(2005)The locomotion of fibroblasts in culture. IV. Electron microscopy of the leading lamella
Exp. Cell Res.
(1971)Confinement and low adhesion induce fast amoeboid migration of slow mesenchymal cells
Cell
(2015)Cortical contractility triggers a stochastic switch to fast amoeboid cell motility
Cell
(2015)Dimensions in cell migration
Curr. Opin. Cell Biol.
(2013)Contact guidance mediated three-dimensional cell migration is regulated by Rho/ROCK-dependent matrix reorganization
Biophys. J.
(2008)3D collagen alignment limits protrusions to enhance breast cancer cell persistence
Biophys. J.
(2014)The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton
J. Biol. Chem.
(2011)
The LINC-less granulocyte nucleus
Eur. J. Cell Biol.
Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration
Cell
Tensile properties of single stress fibers isolated from cultured vascular smooth muscle cells
J. Biomech.
Mechanical modes of ‘amoeboid’ cell migration
Curr. Opin. Cell Biol.
Matrix elasticity directs stem cell lineage specification
Cell
Probing cellular mechanobiology in three-dimensional culture with collagen-agarose matrices
Biomaterials
The behavior of fibroblasts from the developing avian cornea. Morphology and movement in situ and in vitro
J. Cell Biol.
Cell migration: integrating signals from front to back
Science
Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts
J. Cell Sci.
Localized Rac activation dynamics visualized in living cells
Science
Activation of endogenous Cdc42 visualized in living cells
Science
Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia
J. Cell Biol.
Organization of actin in the leading edge of cultured cells: influence of osmium tetroxide and dehydration on the ultrastructure of actin meshworks
J. Cell Biol.
Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells
J. Cell Sci.
Rho-stimulated contractility drives the formation of stress fibers and focal adhesions
J. Cell Biol.
mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration
J. Cell Sci.
Mechanism of retraction of the trailing edge during fibroblast movement
J. Cell Biol.
Segregation and activation of myosin IIB creates a rear in migrating cells
J. Cell Biol.
Membrane insertion at the leading-edge of motile fibroblasts
Proc. Natl. Acad. Sci. U.S.A.
Cdc42 localization and cell polarity depend on membrane traffic
J. Cell Biol.
At the leading edge of three-dimensional cell migration
J. Cell Sci.
Nonpolarized signaling reveals two distinct modes of 3D cell migration
J. Cell Biol.
Blebs lead the way: how to migrate without lamellipodia
Nat. Rev. Mol. Cell Biol.
Rapid leukocyte migration by integrin-independent flowing and squeezing
Nature
Cited by (74)
Ultra-low content physio-chemically crosslinked gelatin hydrogel improves encapsulated 3D cell culture
2024, International Journal of Biological MacromoleculesModulation of cell migration and cell tracking of the gilthead seabream (Sparus aurata) SAF-1 cells by probiotics
2023, Fish and Shellfish ImmunologyFilopodia and Lamellipodia
2022, Encyclopedia of Cell Biology: Volume 1-6, Second EditionFundamental mechanics of cell shape and cell movement
2022, Cell Movement in Health and DiseaseJamming and arrest of cell motion in biological tissues
2021, Current Opinion in Cell BiologyA Microfluidic Perfusion Culture Setup to Investigate Cell Migration in 3D Constrictions
2024, Advanced Materials Technologies