scholarly journals Anisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Arja Ray ◽  
Oscar Lee ◽  
Zaw Win ◽  
Rachel M. Edwards ◽  
Patrick W. Alford ◽  
...  
Keyword(s):  
Cell Migration ◽  
Focal Adhesions ◽  
Contact Guidance ◽  
Directed Cell Migration

scholarly journals Adenomatous polyposis coli nucleates actin assembly to drive cell migration and microtubule-induced focal adhesion turnover

2017 ◽  
Vol 216 (9) ◽  
pp. 2859-2875 ◽  
Author(s):  
M. Angeles Juanes ◽  
Habib Bouguenina ◽  
Julian A. Eskin ◽  
Richa Jaiswal ◽  
Ali Badache ◽  
...  
Keyword(s):  
Cell Migration ◽  
Adenomatous Polyposis Coli ◽  
Focal Adhesions ◽  
Adenomatous Polyposis ◽  
Actin Assembly ◽  
Polyposis Coli ◽  
Directed Cell Migration ◽  
Direct Cell ◽  
Mitochondrial Distribution

Cell motility depends on tight coordination between the microtubule (MT) and actin cytoskeletons, but the mechanisms underlying this MT–actin cross talk have remained poorly understood. Here, we show that the tumor suppressor protein adenomatous polyposis coli (APC), which is a known MT-associated protein, directly nucleates actin assembly to promote directed cell migration. By changing only two residues in APC, we generated a separation-of-function mutant, APC (m4), that abolishes actin nucleation activity without affecting MT interactions. Expression of full-length APC carrying the m4 mutation (APC (m4)) rescued cellular defects in MT organization, MT dynamics, and mitochondrial distribution caused by depletion of endogenous APC but failed to restore cell migration. Wild-type APC and APC (m4) localized to focal adhesions (FAs), and APC (m4) was defective in promoting actin assembly at FAs to facilitate MT-induced FA turnover. These results provide the first direct evidence for APC-mediated actin assembly in vivo and establish a role for APC in coordinating MTs and actin at FAs to direct cell migration.

scholarly journals Force Fluctuations within Focal Adhesions Mediate ECM-Rigidity Sensing to Guide Directed Cell Migration

Cell ◽  
2012 ◽  
Vol 151 (7) ◽  
pp. 1513-1527 ◽  
Author(s):  
Sergey V. Plotnikov ◽  
Ana M. Pasapera ◽  
Benedikt Sabass ◽  
Clare M. Waterman
Keyword(s):  
Cell Migration ◽  
Focal Adhesions ◽  
Force Fluctuations ◽  
Rigidity Sensing ◽  
Directed Cell Migration

scholarly journals Three-dimensional Cancer Cell Migration Directed by Dual Mechanochemical Guidance

2021 ◽  
Author(s):  
Pedram Esfahani ◽  
Herbert Levine ◽  
Mrinmoy Mukherjee ◽  
Bo Sun
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Three Dimensional ◽  
Contact Guidance ◽  
Chemical Gradient ◽  
Cell Microenvironment ◽  
Directed Cell Migration ◽  
The Impact ◽  
Cell Mechanosensing

Directed cell migration guided by external cues plays a central role in many physiological and pathophysiological processes. The microenvironment of cells often simultaneously contains various cues and the motility response of cells to multiplexed guidance is poorly understood. Here we combine experiments and mathematical models to study the three-dimensional migration of breast cancer cells in the presence of both contact guidance and a chemoattractant gradient. We find that the chemotaxis of cells is complicated by the presence of contact guidance as the microstructure of extracellular matrix (ECM) vary spatially. In the presence of dual guidance, the impact of ECM alignment is determined externally by the coherence of ECM fibers, and internally by cell mechanosensing Rho/Rock pathways. When contact guidance is parallel to the chemical gradient, coherent ECM fibers significantly increase the efficiency of chemotaxis. When contact guidance is perpendicular to the chemical gradient, cells exploit the ECM disorder to locate paths for chemotaxis. Our results underscores the importance of fully characterizing the cancer cell microenvironment in order to better understand invasion and metastasis.

scholarly journals Mechanosensing during directed cell migration requires dynamic actin polymerization at focal adhesions

2019 ◽  
Vol 218 (12) ◽  
pp. 4215-4235 ◽  
Author(s):  
Julieann I. Puleo ◽  
Sara S. Parker ◽  
Mackenzie R. Roman ◽  
Adam W. Watson ◽  
Kiarash Rahmani Eliato ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Focal Adhesions ◽  
Mechanical Stimuli ◽  
Matrix Stiffness ◽  
Cellular Behavior ◽  
Cytoskeletal Remodeling ◽  
Cell Matrix ◽  
Directed Cell Migration ◽  
Cell Matrix Adhesion

The mechanical properties of a cell’s microenvironment influence many aspects of cellular behavior, including cell migration. Durotaxis, the migration toward increasing matrix stiffness, has been implicated in processes ranging from development to cancer. During durotaxis, mechanical stimulation by matrix rigidity leads to directed migration. Studies suggest that cells sense mechanical stimuli, or mechanosense, through the acto-myosin cytoskeleton at focal adhesions (FAs); however, FA actin cytoskeletal remodeling and its role in mechanosensing are not fully understood. Here, we show that the Ena/VASP family member, Ena/VASP-like (EVL), polymerizes actin at FAs, which promotes cell-matrix adhesion and mechanosensing. Importantly, we show that EVL regulates mechanically directed motility, and that suppression of EVL expression impedes 3D durotactic invasion. We propose a model in which EVL-mediated actin polymerization at FAs promotes mechanosensing and durotaxis by maturing, and thus reinforcing, FAs. These findings establish dynamic FA actin polymerization as a central aspect of mechanosensing and identify EVL as a crucial regulator of this process.

Engineering Tools for Studying Coordination Between Biochemical and Biomechanical Activities in Cell Migration

2011 ◽  
Author(s):  
Sungsoo Na
Keyword(s):  
Cell Migration ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Resonance Energy Transfer ◽  
Focal Adhesions ◽  
Resonance Energy ◽  
Leading Edge ◽  
Dynamic Feedback ◽  
Chemical Signaling ◽  
Directed Cell Migration

Cell migration is achieved by the dynamic feedback interactions between traction forces generated by the cell and exerted onto the underlying extracellular matrix (ECM), and intracellular mechano-chemical signaling pathways, e.g., Rho GTPase (RhoA, Rac1, and Cdc42) activities [1,2,3]. These components are differentially distributed within a cell, and thus the coordination between tractions and mechanotransduction (i.e, RhoA and Rac1 activities) must be implemented at a precise spatial and temporal order to achieve optimized, directed cell migration [4,5]. Recent studies have shown that focal adhesions at the leading edge exert strong tractions [6], and these traction sites are co-localized with focal adhesion sites [7]. Further, by using the fluorescence resonance energy transfer (FRET) technology coupled with genetically encoded biosensors, researchers reported that Rho GTPases, such as RhoA [8], Rac1 [9], and Cdc42 [10] are maximally activated at the leading edge, suggesting the leading edge of the cell as its common functional site for Rho GTPase activities. All these works, however, were done separately, and the relationship between tractions and mechanotransduction during cell migration has not been demonstrated directly because of the difficulty in simultaneously recording tractions and mechanotransduction in migrating cells, precluding direct comparison between these results. Furthermore, these studies have been conducted by monitoring cells on glass coverslips, the stiffness of which is ∼ 65 giga pascal (GPa), at least three to six order higher than the physiological range of ECM stiffness. Although it is increasingly accepted that ECM stiffness influences cell migration, it is not known exactly how physiologically relevant ECM stiffness (order of kPa range) affects the dynamics of RhoA and Rac1 activities. For a complete understanding of the mechanism of mechano-chemical signaling in the context of cell migration, the dynamics and interplay between biomechanical (e.g., tractions) and biochemical (e.g., Rho GTPase) activities should be visualized within the physiologically relevant range of ECM stiffness.

scholarly journals Comparative study of extracellular fibrils on the ectodermal layer in gastrulae of five amphibian species

1983 ◽  
Vol 59 (1) ◽  
pp. 61-70
Author(s):  
N. Nakatsuji ◽  
K.E. Johnson
Keyword(s):  
Cell Migration ◽  
Rana Pipiens ◽  
Ambystoma Maculatum ◽  
Contact Guidance ◽  
Amphibian Species ◽  
Animal Pole ◽  
Dense Networks ◽  
Directed Cell Migration ◽  
Inner Surface ◽  
Extracellular Fibrils

Previous studies have shown the presence of a network of extracellular fibrils on the inner surface of the ectodermal layer of the Ambystoma maculatum gastrulae. The alignment of the network along the blastopore-animal pole axis has suggested that the network of fibrils guides the migrating mesodermal cells in gastrulae by contact guidance. We have also shown that these fibrils can be deposited on substrata by explanted embryonic fragments and that substrata conditioned in this manner support directed cell migration. In this study, we found that the appearance of the fibrils in the embryos coincides with the start of cell migration towards the animal pole. Gastrulae of three urodele species examined (A. maculatum, A. mexicanum and Cynops pyrrhogaster) have similar dense networks of fibrils. Xenopus laevis gastrulae also have similar fibrils but fewer fibrils compared to urodele embryos. Rana pipiens gastrulae have very few extracellular fibrils. The scarcity of the fibrils in anuran species may be related to the differences in arrangement of mesodermal cells during migration.

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