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

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Lyp/PTPN22 is a negative regulator of integrin mediated T cell adhesion and migration; the disease associated PTPN22 allelic variant is a loss of function mutant that perturbs T cell migration

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.149096.16 ◽

2011 ◽

Vol 70 (Suppl 2) ◽

pp. A7-A7 ◽

Cited By ~ 3

Author(s):

L. Svensson ◽

G. Burn ◽

C. Sanchez-Blanco ◽

R. Zamoyska ◽

A. Cope

Keyword(s):

Cell Migration ◽

Cell Adhesion ◽

T Cell ◽

Allelic Variant ◽

Negative Regulator ◽

Loss Of Function ◽

T Cell Migration ◽

Cell Adhesion And Migration ◽

And Migration ◽

T Cell Adhesion

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

PLoS ONE ◽

10.1371/journal.pone.0257495 ◽

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.

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FAK and paxillin

The Journal of Cell Biology ◽

10.1083/jcb.200406151 ◽

2004 ◽

Vol 166 (2) ◽

pp. 157-159 ◽

Cited By ~ 67

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.

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RET-Mediated Cell Adhesion and Migration Require Multiple Integrin Subunits

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-0771 ◽

2010 ◽

Vol 95 (11) ◽

pp. E342-E346 ◽

Cited By ~ 17

Author(s):

Jessica G. Cockburn ◽

Douglas S. Richardson ◽

Taranjit S. Gujral ◽

Lois M. Mulligan

Keyword(s):

Cell Migration ◽

Cell Adhesion ◽

Cell Line ◽

Adhesion Formation ◽

Xenograft Model ◽

Tumor Xenograft ◽

Mouse Tumor ◽

Cell Adhesion And Migration ◽

And Migration

Context: The RET receptor tyrosine kinase is an important mediator of several human diseases, most notably of neuroendocrine cancers. These diseases are characterized by aberrant cell migration, a process tightly regulated by integrins. Objective: Our goals were to investigate the role of integrins in RET-mediated migration in two neoplastic cell models: the neural-derived cell line SH-SY5Y, and the papillary thyroid carcinoma cell line TPC-1. We also evaluated whether multiple integrin subunits have a role in RET-mediated cell migration. Design: We evaluated the expression and activation of integrins in response to RET activation using standard cell adhesion and migration (wound-healing) assays. We examined focal adhesion formation, using integrin-paxillin coimmunoprecipitations and immunofluorescence, as an indicator of integrin activity. Results: Our data indicate that β1 integrin (ITGB1) is expressed in both SH-SY5Y and TPC-1 cell lines and that these cells adhere strongly to matrices preferentially associated with ITGB1. We showed that RET can activate ITGB1, and that RET-induced cell adhesion and migration require ITGB1. Furthermore, we showed that β3 integrin (ITGB3) also plays a role in RET-mediated cell adhesion and migration in vitro and ITGB3 expression correlates with RET-mediated invasion in a mouse tumor xenograft model, suggesting that RET mediates the activity of multiple integrin subunits. Conclusions: Our data are the first to show that multiple integrin subunits contribute to cell adhesion and migration downstream of RET, suggesting that coordinated signaling through these pathways is important for cell interactions with the microenvironment during tumor invasion and progression.

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Engineered Fibrillar Extracellular Matrices for the Study of Directed Cell Migration

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80943 ◽

2012 ◽

Author(s):

Brendon M. Baker ◽

Colin K. Choi ◽

Britta Trappmann ◽

Christopher S. Chen

Keyword(s):

Cell Migration ◽

Cell Adhesion ◽

The Body ◽

Collagen Gels ◽

Connective Tissues ◽

Structural Anisotropy ◽

Flat Surfaces ◽

Cell Adhesion And Migration ◽

And Migration

The biology of cell adhesion and migration has traditionally been studied on 2D glass or plastic surfaces. While such studies have shed light on the molecular mechanisms governing these processes [1], current knowledge is limited by the dissimilarity between the flat surfaces conventionally employed and the topographically complex extracellular matrix (ECM) cells routinely navigate within the body. On ECM-coated flat surfaces, cells are presented with an unlimited expanse of adhesive ligand and can spread and migrate freely. Conversely, the availability of ligand in vivo is generally restricted to ECM structures, forcing cells to form adhesions in prescribed locations distributed through 3D space depending on the geometry and organization of the surrounding matrix [2]. These physical constraints on cell adhesion likely have profound consequences on intracellular signaling and resulting migration, and calls into question whether the mechanisms and modes of cell motility observed on flat substrates are truly reflective of the in vivo scenario [3]. The topographies of ECMs found in vivo are varied but largely fibrillar, ranging from the tightly crosslinked fibers that form the sheet-like basement membrane, to the structure of fibrin-rich clots and collagenous connective tissues. Collagen comprises approximately 25% of the human body by mass, and as such, purified collagen has served as a popular setting for the study of cell migration within a fibrillar context for many decades [4]. However, a major limitation to the use of these gels is the inability to orthogonally dictate key structural features that impact cell behavior. For example, in contrast to the large range of fiber diameters found in vivo within connective tissue resulting from hierarchical collagen assembly and multiple types of collagens [3], collagen gels are limited to fibril diameters of ∼500nm. Furthermore, recreating the structural anisotropy common to connective tissues in collagen gels is technically challenging [5]. Thus, there remains a significant need for engineered fibrillar materials that afford precise and independent control of architectural and mechanical features for application in cell biology. In this work, we develop two approaches to fabricating fibrillar ECMs in order to study cell adhesion and migration in vitro.

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Specific roles of the alpha V beta 1, alpha V beta 3 and alpha V beta 5 integrins in avian neural crest cell adhesion and migration on vitronectin

Development ◽

10.1242/dev.120.9.2687 ◽

1994 ◽

Vol 120 (9) ◽

pp. 2687-2702 ◽

Cited By ~ 5

Author(s):

M. Delannet ◽

F. Martin ◽

B. Bossy ◽

D.A. Cheresh ◽

L.F. Reichardt ◽

...

Keyword(s):

Cell Migration ◽

Cell Adhesion ◽

Neural Crest ◽

Neural Crest Cell ◽

Neural Crest Cells ◽

Cell Adhesion And Migration ◽

And Migration ◽

Alpha V Beta 3 ◽

Crest Cell

To identify potentially important extracellular matrix adhesive molecules in neural crest cell migration, the possible role of vitronectin and its corresponding integrin receptors was examined in the adhesion and migration of avian neural crest cells in vitro. Adhesion and migration on vitronectin were comparable to those found on fibronectin and could be almost entirely abolished by antibodies against vitronectin and by RGD peptides. Immunoprecipitation and immunocytochemistry analyses revealed that neural crest cells expressed primarily the alpha V beta 1, alpha V beta 3 and alpha V beta 5 integrins as possible vitronectin receptors. Inhibition assays of cellular adhesion and migration with function-perturbing antibodies demonstrated that adhesion of neural crest cells to vitronectin was mediated essentially by one or more of the different alpha V integrins, with a possible preeminence of alpha V beta 1, whereas cell migration involved mostly the alpha V beta 3 and alpha V beta 5 integrins. Immunofluorescence labeling of cultured motile neural crest cells revealed that the alpha V integrins are differentially distributed on the cell surface. The beta 1 and alpha V subunits were both diffuse on the surface of cells and in focal adhesion sites in association with vinculin, talin and alpha-actinin, whereas the alpha V beta 3 and alpha V beta 5 integrins were essentially diffuse on the cell surface. Finally, vitronectin could be detected by immunoblotting and immunohistochemistry in the early embryo during the ontogeny of the neural crest. It was in particular closely associated with the surface of migrating neural crest cells. In conclusion, our study indicates that neural crest cells can adhere to and migrate on vitronectin in vitro by an RGD-dependent mechanism involving at least the alpha V beta 1, alpha V beta 3 and alpha V beta 5 integrins and that these integrins may have specific roles in the control of cell adhesion and migration.

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