scholarly journals Balance between cell−substrate adhesion and myosin contraction determines the frequency of motility initiation in fish keratocytes

2015 ◽  
Vol 112 (16) ◽  
pp. 5045-5050 ◽  
Author(s):  
Erin Barnhart ◽  
Kun-Chun Lee ◽  
Greg M. Allen ◽  
Julie A. Theriot ◽  
Alex Mogilner
Keyword(s):  
Symmetry Breaking ◽  
Spontaneous Symmetry Breaking ◽  
Adhesion Strength ◽  
Network Flow ◽  
Critical Threshold ◽  
Stable States ◽  
Flow Rates ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Substrate Adhesion

Cells are dynamic systems capable of spontaneously switching among stable states. One striking example of this is spontaneous symmetry breaking and motility initiation in fish epithelial keratocytes. Although the biochemical and mechanical mechanisms that control steady-state migration in these cells have been well characterized, the mechanisms underlying symmetry breaking are less well understood. In this work, we have combined experimental manipulations of cell−substrate adhesion strength and myosin activity, traction force measurements, and mathematical modeling to develop a comprehensive mechanical model for symmetry breaking and motility initiation in fish epithelial keratocytes. Our results suggest that stochastic fluctuations in adhesion strength and myosin localization drive actin network flow rates in the prospective cell rear above a critical threshold. Above this threshold, high actin flow rates induce a nonlinear switch in adhesion strength, locally switching adhesions from gripping to slipping and further accelerating actin flow in the prospective cell rear, resulting in rear retraction and motility initiation. We further show, both experimentally and with model simulations, that the global levels of adhesion strength and myosin activity control the stability of the stationary state: The frequency of symmetry breaking decreases with increasing adhesion strength and increases with increasing myosin contraction. Thus, the relative strengths of two opposing mechanical forces—contractility and cell−substrate adhesion—determine the likelihood of spontaneous symmetry breaking and motility initiation.

Integrin-Mediated Fibroblast Adhesion Strength: Role of the β1 Subunit

1993 ◽  
Vol 331 ◽  
Author(s):  
Kelly A. Ward ◽  
Jun-Lin Guan ◽  
Daniel A. Hammer
Keyword(s):  
Extracellular Matrix ◽  
Adhesion Strength ◽  
Cytoplasmic Domain ◽  
Integrin Receptors ◽  
Substrate Adhesion ◽  
Focal Contacts ◽  
Cell Substrate ◽  
Extracellular Matrix Molecules ◽  
Integrin Ligand ◽  
Cell Substrate Adhesion

AbstractCell-substratum adhesion is important in wound healing [4], embryogenic development [11], tissue architecture [6], and metastasis [7]. Integrins constitute a major class of heterodimeric cell-surface glycoproteins involved in receptor-mediated adhesion to the extracellular matrix (ECM). Focal contacts are regions of the cell-substratum adhesion in which clusters of integrin receptors connect the cytoskeleton to extracellular matrix molecules such as fibronectin. Focal contacts strengthen cell-substrate adhesion, and are sites of biochemical activity. Since cell adhesion strength in part depends on the cell's ability to cluster receptors and cytoskeleton into focal contacts, the integrity of the focal contact, and hence a cell's adhesive strength, will depend both on integrin-cytoskeletal binding as well as integrin-ligand binding.Using a centrifugation assay, we have quantified cell-substratum adhesion strength of mouse 3T3 cells transfected with the avian β1 integrin receptor (wild type), including various deletion mutants of its cytoplasmic domain, to surfaces containing varying concentrations of CSAT, a monoclonal antibody against the extracellular domain of the avian β1 subunit. For all the transfectants, adhesion strength decreases with decreasing CSAT concentration and increasing centrifugal strength. Different truncations of the cytoplasmic domain lead to different levels of adhesion. There is no simple correlation between the length of the cytoplasmic domain and the strength of adhesion.

scholarly journals Symmetry breaking transition towards directional locomotion in Physarum microplasmodia

2019 ◽  
Author(s):  
Shun Zhang ◽  
Juan C. Lasheras ◽  
Juan C. del Álamo
Keyword(s):  
Symmetry Breaking ◽  
Physarum Polycephalum ◽  
Model Organism ◽  
Dominant Mode ◽  
Interfacial Instability ◽  
Amoeboid Locomotion ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Rear Part ◽  
Cell Substrate Adhesion

AbstractTrue slime mold Physarum polycephalum has been widely used as a model organism to study flow-driven amoeboid locomotion as well as the dynamics of its complex mechanochemical self-oscillations. The aim of this work is to quantify the mechanical aspects of symmetry breaking and its transition into directional flow-driven amoeboid locomotion in small (<∼ 200 µm) fragments of Physarum polycephalum. To this end, we combined measurements of traction stresses, fragment morphology, and ectoplasmic microrheology with experimental manipulations of cell-substrate adhesion, cortical strength and microplasmodium size. These measurements show that initiation of locomotion is accompanied by the symmetry breaking of traction stresses and the polarization of ectoplasmic mechanical properties, with the rear part of the microplasmodium becoming significantly stiffer after the onset of locomotion. Our experimental data suggests that the initiation of locomotion in Physarum could be analogous to an interfacial instability process and that microplasmodial size is a critical parameter governing the instability. Specifically, our results indicate that the instability driving the onset of locomotion is strengthened by substrate adhesiveness and weakened by cortical stiffness. Furthermore, the Fourier spectral analysis of morphology revealed lobe number n = 2 as the consistent dominant mode number across various experimental manipulations, suggesting that the instability mechanism driving the onset of Physarum locomotion is robust with respect to changes in environmental conditions and microplasmodial properties.

scholarly journals Regulation of cell-substrate adhesion by proteoglycans immobilized on extracellular substrates

1989 ◽  
Vol 264 (14) ◽  
pp. 8012-8018 ◽  
Author(s):  
M Yamagata ◽  
S Suzuki ◽  
S K Akiyama ◽  
K M Yamada ◽  
K Kimata
Keyword(s):  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Substrate Adhesion

scholarly journals A GTPase controls cell-substrate adhesion in Xenopus XTC fibroblasts.

1992 ◽  
Vol 118 (5) ◽  
pp. 1235-1244 ◽  
Author(s):  
M H Symons ◽  
T J Mitchison
Keyword(s):  
Control Cell ◽  
Response To Treatment ◽  
Nucleotide Analogs ◽  
Cell Contractility ◽  
Cell Rounding ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Adhesive Interactions ◽  
Cell Substrate Adhesion ◽  
Gamma S

Cell-substrate adhesion is crucial at various stages of development and for the maintenance of normal tissues. Little is known about the regulation of these adhesive interactions. To investigate the role of GTPases in the control of cell morphology and cell-substrate adhesion we have injected guanine nucleotide analogs into Xenopus XTC fibroblasts. Injection of GTP gamma S inhibited ruffling and increased spreading, suggesting an increase in adhesion. To further investigate this, we made use of GRGDSP, a peptide which inhibits binding of integrins to vitronectin and fibronectin. XTC fibroblasts injected with non-hydrolyzable analogs of GTP took much more time to round up than mock-injected cells in response to treatment with GRGDSP, while GDP beta S-injected cells rounded up in less time than controls. Injection with GTP gamma S did not inhibit cell rounding induced by trypsin however, showing that cell contractility is not significantly affected by the activation of GTPases. These data provide evidence for the existence of a GTPase which can control cell-substrate adhesion from the cytoplasm. Treatment of XTC fibroblasts with the phorbol ester 12-o-tetradecanoylphorbol-13-acetate reduced cell spreading and accelerated cell rounding in response to GRGDSP, which is essentially opposite to the effect exerted by non-hydrolyzable GTP analogs. These results suggest the existence of at least two distinct pathways controlling cell-substrate adhesion in XTC fibroblasts, one depending on a GTPase and another one involving protein kinase C.

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