A Multiscale Model of Cell Adhesion and Migration on Extracellular Matrices of Defined Stiffness and Adhesivity

2011 ◽  
Author(s):  
Amit Pathak ◽  
Sanjay Kumar
Keyword(s):  
Cell Migration ◽  
Tumor Invasion ◽  
Multiscale Model ◽  
Extracellular Matrices ◽  
Eukaryotic Cells ◽  
Biophysical Properties ◽  
Invasion And Metastasis ◽  
Ligand Density ◽  
Cell Adhesion And Migration ◽  
And Migration

Eukaryotic cells actively respond to variations in ligand density and stiffness of their extracellular matrix (ECM). This cell-ECM relationship plays an important role in regulating cell migration, wound healing, tumor invasion and metastasis. A better understanding of these mechanosenstive responses requires more rigorous models of the relationships between ECM biophysical properties, mechanotransductive signals, assembly of contractile and adhesive structures, and cell migration.

scholarly journals Guiding cell adhesion and motility by modulating cross-linking and topographic properties of microgel arrays

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257495
Author(s):  
Janine Riegert ◽  
Alexander Töpel ◽  
Jana Schieren ◽  
Renee Coryn ◽  
Stella Dibenedetto ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Focal Adhesion ◽  
Sertoli Cells ◽  
Cellular Systems ◽  
Cross Linking ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
The Impact

Biomaterial-driven modulation of cell adhesion and migration is a challenging aspect of tissue engineering. Here, we investigated the impact of surface-bound microgel arrays with variable geometry and adjustable cross-linking properties on cell adhesion and migration. We show that cell migration is inversely correlated with microgel array spacing, whereas directionality increases as array spacing increases. Focal adhesion dynamics is also modulated by microgel topography resulting in less dynamic focal adhesions on surface-bound microgels. Microgels also modulate the motility and adhesion of Sertoli cells used as a model for cell migration and adhesion. Both focal adhesion dynamics and speed are reduced on microgels. Interestingly, Gas2L1, a component of the cytoskeleton that mediates the interaction between microtubules and microfilaments, is dispensable for the regulation of cell adhesion and migration on microgels. Finally, increasing microgel cross-linking causes a clear reduction of focal adhesion turnover in Sertoli cells. These findings not only show that spacing and rigidity of surface-grafted microgels arrays can be effectively used to modulate cell adhesion and motility of diverse cellular systems, but they also form the basis for future developments in the fields of medicine and tissue engineering.

scholarly journals Cis-Dimerization Mediates Function of Junctional Adhesion Molecule A

2008 ◽  
Vol 19 (5) ◽  
pp. 1862-1872 ◽  
Author(s):  
Eric A. Severson ◽  
Liangyong Jiang ◽  
Andrei I. Ivanov ◽  
Kenneth J. Mandell ◽  
Asma Nusrat ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Adhesion Molecule ◽  
Protein Localization ◽  
Binding Motif ◽  
Β1 Integrin ◽  
Mrna Levels ◽  
Functional Link ◽  
Cell Adhesion And Migration ◽  
And Migration

Junctional adhesion molecule-A (JAM-A) is a transmembrane component of tight junctions that has been proposed to play a role in regulating epithelial cell adhesion and migration, yet mechanistic structure–function studies are lacking. Although biochemical and structural studies indicate that JAM-A forms cis-homodimers, the functional significance of dimerization is unclear. Here, we report the effects of cis-dimerization–defective JAM-A mutants on epithelial cell migration and adhesion. Overexpression of dimerization-defective JAM-A mutants in 293T cells inhibited cell spreading and migration across permeable filters. Similar inhibition was observed with using dimerization-blocking antibodies. Analyses of cells expressing the JAM-A dimerization-defective mutant proteins revealed diminished β1 integrin protein but not mRNA levels. Further analyses of β1 protein localization and expression after disruption of JAM-A dimerization suggested that internalization of β1 integrin precedes degradation. A functional link between JAM-A and β1 integrin was confirmed by restoration of cell migration to control levels after overexpression of β1 integrin in JAM-A dimerization-defective cells. Last, we show that the functional effects of JAM dimerization require its carboxy-terminal postsynaptic density 95/disc-large/zonula occludins-1 binding motif. These results suggest that dimerization of JAM-A regulates cell migration and adhesion through indirect mechanisms involving posttranscriptional control of β1 integrin levels.

Truncation of MYH8 tail in AML: a novel prognostic marker with increase cell migration and epithelial–mesenchymal transition utilizing RAF/MAPK pathway

2019 ◽  
Vol 41 (6) ◽  
pp. 817-827 ◽  
Author(s):  
Hyejoo Park ◽  
Daeyoon Kim ◽  
Dongchan Kim ◽  
Jihyun Park ◽  
Youngil Koh ◽  
...  
Keyword(s):  
Cell Migration ◽  
Prognostic Marker ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Mapk Pathway ◽  
Adhesion Assay ◽  
Genome Database ◽  
Mesenchymal Transition ◽  
Cell Adhesion And Migration ◽  
And Migration

Abstract MYH8 is an actin-based motor protin involved in integrin-mediated cell adhesion and migration. Heretofore, the association of MYH8 mutation and cancer is unclear. In this study, we investigated the biologic significance of novel MYH8 tail truncation mutation, R1292X, in acute myeloid leukemia (AML) which was discovered by whole-exome sequencing and targeted re-sequencing of 209 AML patients. The patients harboring the mutation all relapsed within 3.8–20.9 months. To explore the functional consequence of the mutation in AML progress, we established knock-in cell lines using CRISPR-Cas9 genome editing. Using the established mutant model, we assessed traits of cancer progress. The mutant cells had improved motility, which was confirmed by immunofluorescence staining, wound healing, transwell migration and adhesion assay. The cell morphology and cell cycle were altered to be accessible to migration and epithelial-to-mesenchymal transition (EMT) transcription factors were also increased. The Raf and p44/42 MAPK pathway was a major regulator of these characteristics proved by a screening of signal transduction and inhibitor assay. Further, a public cancer genome database (cBioPortal) shows that MYH8 tail truncation mutations occurring near the R1292 position of the genome may have a significant function in cancer. In conclusion, truncation of MYH8 could be a novel prognostic marker related to poor prognosis by inducing cell migration and EMT features, and inhibition of the Raf/MAPK pathway would be a therapeutic strategy for AML patients with MYH8 tail truncation.

scholarly journals A mode of cell adhesion and migration facilitated by CD44-dependent microtentacles

2020 ◽  
Vol 117 (21) ◽  
pp. 11432-11443 ◽  
Author(s):  
Kayla J. Wolf ◽  
Poojan Shukla ◽  
Kelsey Springer ◽  
Stacey Lee ◽  
Jason D. Coombes ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Brain Slices ◽  
Connective Tissues ◽  
Superresolution Imaging ◽  
Culture Models ◽  
Cell Adhesion And Migration ◽  
Direct Cell ◽  
And Migration ◽  
The Brain ◽  
Organotypic Brain Slices

The structure and mechanics of many connective tissues are dictated by a collagen-rich extracellular matrix (ECM), where collagen fibers provide topological cues that direct cell migration. However, comparatively little is known about how cells navigate the hyaluronic acid (HA)-rich, nanoporous ECM of the brain, a problem with fundamental implications for development, inflammation, and tumor invasion. Here, we demonstrate that glioblastoma cells adhere to and invade HA-rich matrix using microtentacles (McTNs), which extend tens of micrometers from the cell body and are distinct from filopodia. We observe these structures in continuous culture models and primary patient-derived tumor cells, as well as in synthetic HA matrix and organotypic brain slices. High-magnification and superresolution imaging reveals McTNs are dynamic, CD44-coated tubular protrusions containing microtubules and actin filaments, which respectively drive McTN extension and retraction. Molecular mechanistic studies reveal that McTNs are stabilized by an interplay between microtubule-driven protrusion, actomyosin-driven retraction, and CD44-mediated adhesion, where adhesive and cytoskeletal components are mechanistically coupled by an IQGAP1–CLIP170 complex. McTNs represent a previously unappreciated mechanism through which cells engage nanoporous HA matrix and may represent an important molecular target in physiology and disease.

MECHANICS IN MECHANOSENSITIVITY OF CELL ADHESION AND ITS ROLES IN CELL MIGRATION

2012 ◽  
Vol 01 (04) ◽  
pp. 1250032 ◽  
Author(s):  
YUAN ZHONG ◽  
SHIJIE HE ◽  
BAOHUA JI
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Traction Force ◽  
Coupling Model ◽  
Cell Traction ◽  
Chemical Coupling ◽  
Cell Adhesion And Migration ◽  
Cell Front ◽  
Sense And Respond ◽  
And Migration

Cells sense and respond to external stimuli and properties of their environment through focal adhesion complexes (FACs) to regulate a broad range of physiological and pathological processes, including cell migration. Currently, the basic principles in mechanics of the mechanosensitivity of cell adhesion and migration have not been fully understood. In this paper, an FEM-based mechano-chemical coupling model is proposed for studying the cell migration behaviors in which the dynamics of stability of FACs and the effect of cell shape on cell traction force distribution are considered. We find that the driving force of cell migration is produced by the competition of stability of cell adhesion between the cell front and cell rear, which consequently controls the speed of cell migration. We show that the rigidity gradient of matrix can bias this competition which allows cell to exhibit a durotaxis behavior, i.e. the larger the gradient, the higher the cell speed.

scholarly journals FAK and paxillin

2004 ◽  
Vol 166 (2) ◽  
pp. 157-159 ◽  
Author(s):  
Michael D. Schaller
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Cell Systems ◽  
Cell Matrix ◽  
Cell Adhesion And Migration ◽  
Positive Regulators ◽  
Cell Adhesions ◽  
And Migration ◽  
New Evidence ◽  
Cell Cell

FAK and paxillin are important components in integrin-regulated signaling. New evidence suggests that these two proteins function in crosstalk between cell–matrix and cell–cell adhesions. Further, new insight suggests that under some conditions these proteins inhibit cell migration, in contrast to their established roles in several cell systems as positive regulators of cell adhesion and migration.

scholarly journals LSP1-myosin1e bi-molecular complex regulates focal adhesion dynamics and cell migration

2020 ◽  
Author(s):  
Katja Schäringer ◽  
Sebastian Maxeiner ◽  
Carmen Schalla ◽  
Stephan Rütten ◽  
Martin Zenke ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Focal Adhesion ◽  
Molecular Complex ◽  
Specific Protein ◽  
Motile Cells ◽  
Associated Proteins ◽  
Cell Adhesion And Migration ◽  
Focal Adhesion Turnover ◽  
And Migration

AbstractSeveral cytoskeleton-associated proteins and signalling pathways work in concert to regulate actin cytoskeleton remodelling, cell adhesion and migration. We have recently demonstrated that the bi-molecular complex between the leukocyte-specific protein 1 (LSP1) and myosin1e controls actin cytoskeleton remodelling during phagocytosis. In this study, we show that LSP1 down regulation severely impairs cell migration, lamellipodia formation and focal adhesion dynamics in macrophages. Inhibition of the interaction between LSP1 and myosin1e also impairs these processes resulting in poorly motile cells, which are characterised by few and small lamellipodia. Furthermore, cells in which LSP1-myosin1e interaction is inhibited are typically associated with inefficient focal adhesion turnover. Collectively, our findings show that the LSP1-myosin1e bimolecular complex plays a pivotal role in the regulation of actin cytoskeleton remodelling and focal adhesion dynamics required for cell migration.

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