scholarly journals Binding of ZO-1 to α5β1 integrins regulates the mechanical properties of α5β1–fibronectin links

2017 ◽  
Vol 28 (14) ◽  
pp. 1847-1852 ◽  
Author(s):  
Víctor González-Tarragó ◽  
Alberto Elosegui-Artola ◽  
Elsa Bazellières ◽  
Roger Oria ◽  
Carlos Pérez-González ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Integrin Α5β1 ◽  
Cell Monolayers ◽  
And Migration ◽  
Integrin Regulation ◽  
In Cells

Fundamental processes in cell adhesion, motility, and rigidity adaptation are regulated by integrin-mediated adhesion to the extracellular matrix (ECM). The link between the ECM component fibronectin (fn) and integrin α5β1 forms a complex with ZO-1 in cells at the edge of migrating monolayers, regulating cell migration. However, how this complex affects the α5β1-fn link is unknown. Here we show that the α5β1/ZO-1 complex decreases the resistance to force of α5β1–fn adhesions located at the edge of migrating cell monolayers while also increasing α5β1 recruitment. Consistently with a molecular clutch model of adhesion, this effect of ZO-1 leads to a decrease in the density and intensity of adhesions in cells at the edge of migrating monolayers. Taken together, our results unveil a new mode of integrin regulation through modification of the mechanical properties of integrin–ECM links, which may be harnessed by cells to control adhesion and migration.

Cell Adhesion

2004 ◽  
Author(s):  
W. Mark Saltzman
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Extracellular Space ◽  
Cell Aggregation ◽  
Solid Substrate ◽  
Cell Interactions ◽  
Phospholipid Bilayer ◽  
Cell Cell

The external surface of the cell consists of a phospholipid bilayer which carries a carbohydrate-rich coat called the glycocalyx; ionizable groups within the glycocalyx, such as sialic acid (N-acetyl neuraminate), contribute a net negative charge to the cell surface. Many of the carbohydrates that form the glycocalyx are bound to membrane-associated proteins. Each of these components— phospholipid bilayer, carbohydrate-rich coat, membrane-associated protein—has distinct physicochemical characteristics and is abundant. Plasma membranes contain ∼50% protein, ∼45% lipid, and ∼5% carbohydrate by weight. Therefore, each component influences cell interactions with the external environment in important ways. Cells can become attached to surfaces. The surface of interest may be geometrically complex (for example, the surface of another cell, a virus, a fiber, or an irregular object), but this chapter will focus on adhesion between a cell and a planar surface. The consequences of cell–cell adhesion are considered further in Chapter 8 (Cell Aggregation and Tissue Equivalents) and Chapter 9 (Tissue Barriers to Molecular and Cellular Transport). The consequences of cell–substrate adhesion are considered further in Chapter 7 (Cell Migration) and Chapter 12 (Cell Interactions with Polymers). Since the growth and function of many tissue-derived cells required attachment and spreading on a solid substrate, the events surrounding cell adhesion are fundamentally important. In addition, the strength of cell adhesion is an important determinant of the rate of cell migration, the kinetics of cell–cell aggregation, and the magnitude of tissue barriers to cell and molecule transport. Cell adhesion is therefore a major consideration in the development of methods and materials for cell delivery, tissue engineering, and tissue regeneration. The most stable and versatile mechanism for cell adhesion involves the specific association of cell surface glycoproteins, called receptors, and complementary molecules in the extracellular space, called ligands. Ligands may exist freely in the extracellular space, they may be associated with the extracellular matrix, or they may be attached to the surface of another cell. Cell–cell adhesion can occur by homophilic binding of identical receptors on different cells, by heterophilic binding of a receptor to a ligand expressed on the surface of a different cell, or by association of two receptors with an intermediate linker. Cell–matrix adhesion usually occurs by heterophilic binding of a receptor to a ligand attached to an insoluble element of the extracellular matrix.

scholarly journals Stiffer Matrix Accelerates Migration of Hepatocellular Carcinoma Cells through Enhanced Aerobic Glycolysis Via the MAPK-YAP Signaling

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 490 ◽  
Author(s):  
Qiu-Ping Liu ◽  
Qing Luo ◽  
Bin Deng ◽  
Yang Ju ◽  
Guan-Bin Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Matrix ◽  
Cell Migration ◽  
Aerobic Glycolysis ◽  
Mapk Signaling ◽  
Carcinoma Cells ◽  
Metabolic Reprogramming ◽  
Signaling Cascade ◽  
And Migration ◽  
Hcc Cells

Increased extracellular matrix (ECM) stiffness and metabolic reprogramming of cancer cells are two fundamental mediators of tumor progression, including hepatocellular carcinoma (HCC). Yet, the correlation between ECM stiffness and excessive aerobic glycolysis in promoting the development of HCC remains unknown. Here, we demonstrated that stiffer ECM promotes HCC cell migration depending on their accelerated aerobic glycolysis. Our results also indicated that stiffer ECM-induced YAP activation plays a major role in promoting aerobic glycolysis of HCC cells. Moreover, we showed that JNK and p38 MAPK signaling are critical for mediating YAP activation in HCC cells. Together, our findings established that the MAPK-YAP signaling cascade that act as a mechanotransduction pathway is essential for promoting HCC cell aerobic glycolysis and migration in response to ECM stiffness.

scholarly journals The L2/HNK-1 carbohydrate of neural cell adhesion molecules is involved in cell interactions.

1988 ◽  
Vol 106 (1) ◽  
pp. 213-223 ◽  
Author(s):  
V Künemund ◽  
F B Jungalwala ◽  
G Fischer ◽  
D K Chou ◽  
G Keilhauer ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Neurite Outgrowth ◽  
Adhesion Molecules ◽  
Neural Cell ◽  
Neural Cells ◽  
Neural Cell Adhesion ◽  
Myelin Associated Glycoprotein ◽  
And Migration ◽  
Straightforward Interpretation

We investigated whether the L2/HNK-1 carbohydrate epitope, expressed by two unusual glycolipids and several neural adhesion molecules, including L1, neural cell adhesion molecule, J1, and the myelin-associated glycoprotein, is involved in adhesion. Monoclonal L2 antibodies, the L2/HNK-1-reactive, sulfate-3-glucuronyl residue carrying glycolipids (L2 glycolipid) and a tetrasaccharide derived from the L2 glycolipid (L2 tetrasaccharide) were added to microexplant cultures of early postnatal mouse cerebellum, and cell migration and process extension were monitored. On the substrate poly-D-lysine, Fab fragments of L2 antibodies, L2 glycolipid, and L2 tetrasaccharide inhibited outgrowth of astrocytic processes and migration of cell bodies, but only L2 glycolipid and L2 tetrasaccharide reduced neurite outgrowth. On laminin, L2 antibodies, L2 glycolipid, and L2 tetrasaccharide inhibited outgrowth of astrocytic processes. Additionally, L2 glycolipid and L2 tetrasaccharide inhibited cell migration and neurite outgrowth. Several negatively charged glycolipids, lipids, and saccharides were tested for control and found to have no effect on outgrowth patterns, except for sulfatide and heparin, which modified outgrowth patterns in a similar fashion as L2 glycolipid and L2 tetrasaccharide. On astrocytes none of the tested compounds interfered with explant outgrowth. In short-term adhesion assays L2 glycolipid, sulfatide, and heparin inhibited adhesion of neural cells to laminin. L2 glycolipid and sulfatide interfered with neuron to astrocyte and astrocyte to astrocyte adhesion, but not with neuron-neuron adhesion. The most straightforward interpretation of these observations is that the L2/HNK-1 carbohydrate and the sulfated carbohydrates, sulfatide and heparin, act as ligands in cell adhesion.

scholarly journals Scribble, Lgl1, and myosin II form a complex in vivo to promote directed cell migration

2020 ◽  
Vol 31 (20) ◽  
pp. 2234-2248
Author(s):  
Maha Abedrabbo ◽  
Shoshana Ravid
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Myosin Ii ◽  
Leading Edge ◽  
Directed Cell Migration ◽  
Lethal Giant Larvae ◽  
And Migration ◽  
Migrating Cells

Here we show that Scribble (Scrib), Lethal giant larvae 1 (Lgl1), and myosin II form a complex in vivo and colocalize at the cell leading edge of migrating cells, and this colocalization is interdependent. Scrib and Lgl1 are required for proper cell adhesion, polarity, and migration.

scholarly journals Mechanosensitive Expression of Lamellipodin Governs Cell Cycle Progression and Intracellular Stiffness

2020 ◽  
Author(s):  
Joseph A. Brazzo ◽  
Kwonmoo Lee ◽  
Yongho Bae
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Cycle Progression ◽  
Cellular Processes ◽  
M Phase ◽  
And Migration ◽  
In Cells

SUMMARYCells exhibit pathological behaviors in response to increased extracellular matrix (ECM) stiffness, including accelerated cell proliferation and migration [1–9], which are correlated with increased intracellular stiffness and tension [2, 3, 10–12]. The biomechanical signal transduction of ECM stiffness into relevant molecular signals and resultant cellular processes is mediated through multiple proteins associated with the actin cytoskeleton in lamellipodia [2, 3, 10, 11, 13]. However, the molecular mechanisms by which lamellipodial dynamics regulate cellular responses to ECM stiffening remain unclear. Previous work described that lamellipodin, a phosphoinositide- and actin filament-binding protein that is known mostly for controlling cell migration [14–21], promotes ECM stiffness-mediated early cell cycle progression [2], revealing a potential commonality between the mechanisms controlling stiffness-dependent cell migration and those controlling cell proliferation. However, i) whether and how ECM stiffness affects the levels of lamellipodin expression and ii) whether stiffness-mediated lamellipodin expression is required throughout cell cycle progression and for intracellular stiffness have not been explored. Here, we show that the levels of lamellipodin expression in cells are significantly increased by a stiff ECM and that this stiffness-mediated lamellipodin upregulation persistently stimulates cell cycle progression and intracellular stiffness throughout the cell cycle, from the early G1 phase to M phase. Finally, we show that both Rac activation and intracellular stiffening are required for the mechanosensitive induction of lamellipodin. More specifically, inhibiting Rac1 activation in cells on stiff ECM reduces the levels of lamellipodin expression, and this effect is reversed by the overexpression of activated Rac1 in cells on soft ECM. We thus propose that lamellipodin is a critical molecular lynchpin in the control of mechanosensitive cell cycle progression and intracellular stiffness.

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 Integrin α5β1 nano-presentation regulates collective keratinocyte migration independent of substrate rigidity

2021 ◽  
Author(s):  
Jacopo Di Russo ◽  
Jennifer L. Young ◽  
Julian W. R. Wegner ◽  
Timmy Steins ◽  
Horst Kessler ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Cell Monolayer ◽  
Collective Cell Migration ◽  
Integrin Α5β1 ◽  
Migration Ability ◽  
Fibronectin Receptor ◽  
Substrate Rigidity ◽  
Scale Properties ◽  
Extracellular Matrix Receptors

AbstractNanometer-scale properties of the extracellular matrix influence many biological processes, including cell motility. While much information is available for single cell migration, to date, no knowledge exists on how the nanoscale presentation of extracellular matrix receptors influences collective cell migration. In wound healing, basal keratinocytes collectively migrate on a fibronectin-rich provisional basement membrane to re-epithelialize the injured skin. Among other receptors, the fibronectin receptor integrin α5β1 plays a pivotal role in this process. Using a highly specific integrin α5β1 peptidomimetic combined with nanopatterned hydrogels, we show that keratinocyte sheets regulate their migration ability at an optimal integrin α5β1 nanospacing. This efficiency relies on the effective propagation of stresses within the cell monolayer independent of substrate stiffness. For the first time, this work highlights the importance of extracellular matrix receptor nanoscale organization required for efficient tissue regeneration.

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