scholarly journals Conditions for optimal mechanical power generation by a bundle of growing actin filaments

2018 ◽  
Author(s):  
Jean-Louis Martiel ◽  
Alphée Michelot ◽  
Rajaa Boujema-Paterski ◽  
Laurent Blanchoin ◽  
Julien Berro
Keyword(s):  
Actin Filaments ◽  
Focal Adhesions ◽  
Mechanical Power ◽  
Biophysical Model ◽  
Physical Factors ◽  
Force Transmission ◽  
Optimum Conditions ◽  
External Forces ◽  
Proper Force

AbstractBundles of actin filaments are central to a large variety of cellular structures, such as filopodia, stress fibers, cytokinetic rings or focal adhesions. The mechanical properties of these bundles are critical for proper force transmission and force bearing. Previous mathematical modeling efforts have focused on bundles’ rigidity and shape. However, it remains unknown how bundle length and thickness are controlled by external physical factors, and how the attachment of the bundle to a load affects its ability to transmit forces. In this paper, we present a biophysical model for dynamic bundles of actin filaments that takes into account individual filaments, their interaction with each other and with an external load. In combination with in vitro motility assays of beads coated with formins, our model allowed us to characterize conditions for bead movement and bundle buckling. From the deformation profiles, we determined key biophysical properties of tethered actin bundles, such as their rigidity and filament density. Our model also demonstrated that filaments undulate under lateral constraints applied by external forces or by neighboring filaments of the bundle. Last, our model allowed us to identify optimum conditions in filament density and barbed end tethering to the load for a maximal yield of mechanical power by a dynamic actin bundle.

scholarly journals Lamellipodin promotes actin assembly by clustering Ena/VASP proteins and tethering them to actin filaments

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Scott D Hansen ◽  
R Dyche Mullins
Keyword(s):  
Axon Guidance ◽  
Actin Filaments ◽  
Network Formation ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Polymerase Activity ◽  
Actin Assembly ◽  
Filament Assembly

Enabled/Vasodilator (Ena/VASP) proteins promote actin filament assembly at multiple locations, including: leading edge membranes, focal adhesions, and the surface of intracellular pathogens. One important Ena/VASP regulator is the mig-10/Lamellipodin/RIAM family of adaptors that promote lamellipod formation in fibroblasts and drive neurite outgrowth and axon guidance in neurons. To better understand how MRL proteins promote actin network formation we studied the interactions between Lamellipodin (Lpd), actin, and VASP, both in vivo and in vitro. We find that Lpd binds directly to actin filaments and that this interaction regulates its subcellular localization and enhances its effect on VASP polymerase activity. We propose that Lpd delivers Ena/VASP proteins to growing barbed ends and increases their polymerase activity by tethering them to filaments. This interaction represents one more pathway by which growing actin filaments produce positive feedback to control localization and activity of proteins that regulate their assembly.

scholarly journals Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcement

2005 ◽  
Vol 171 (2) ◽  
pp. 209-215 ◽  
Author(s):  
Masaaki Yoshigi ◽  
Laura M. Hoffman ◽  
Christopher C. Jensen ◽  
H. Joseph Yost ◽  
Mary C. Beckerle
Keyword(s):  
Shear Stress ◽  
Mechanical Stress ◽  
Actin Filaments ◽  
Focal Adhesions ◽  
Cyclic Stretch ◽  
Stress Fibers ◽  
Focal Adhesion Proteins ◽  
Cytoskeletal Responses ◽  
Actin Stress Fibers

Organs and tissues adapt to acute or chronic mechanical stress by remodeling their actin cytoskeletons. Cells that are stimulated by cyclic stretch or shear stress in vitro undergo bimodal cytoskeletal responses that include rapid reinforcement and gradual reorientation of actin stress fibers; however, the mechanism by which cells respond to mechanical cues has been obscure. We report that the application of either unidirectional cyclic stretch or shear stress to cells results in robust mobilization of zyxin from focal adhesions to actin filaments, whereas many other focal adhesion proteins and zyxin family members remain at focal adhesions. Mechanical stress also induces the rapid zyxin-dependent mobilization of vasodilator-stimulated phosphoprotein from focal adhesions to actin filaments. Thickening of actin stress fibers reflects a cellular adaptation to mechanical stress; this cytoskeletal reinforcement coincides with zyxin mobilization and is abrogated in zyxin-null cells. Our findings identify zyxin as a mechanosensitive protein and provide mechanistic insight into how cells respond to mechanical cues.

scholarly journals Talin at myotendinous junctions.

1986 ◽  
Vol 103 (4) ◽  
pp. 1465-1472 ◽  
Author(s):  
J G Tidball ◽  
T O'Halloran ◽  
K Burridge
Keyword(s):  
Skeletal Muscle ◽  
Actin Filaments ◽  
Skeletal Muscles ◽  
Immunofluorescence Microscopy ◽  
Protein Separations ◽  
Force Transmission ◽  
Electron Microscopic ◽  
Focal Contacts ◽  
Myotendinous Junctions

Junctions formed by skeletal muscles where they adhere to tendons, called myotendinous junctions, are sites of tight adhesion and where forces generated by the cell are placed on the substratum. In this regard, myotendinous junctions and focal contacts of fibroblasts in vitro are analogues. Talin is a protein located at focal contacts that may be involved in force transmission from actin filaments to the plasma membrane. This study investigates whether talin is also found at myotendinous junctions. Protein separations on SDS polyacrylamide gels and immunolabeling procedures show that talin is present in skeletal muscle. Immunofluorescence microscopy using anti-talin indicates that talin is found concentrated at myotendinous junctions and in lesser amounts in periodic bands over nonjunctional regions. Electron microscopic immunolabeling shows talin is a component of the digitlike processes of muscle cells that extend into tendons at myotendinous junctions. These findings indicate that there may be similarities in the molecular composition of focal contacts and myotendinous junctions in addition to functional analogies.

scholarly journals mDia1 Targets v-Src to the Cell Periphery and Facilitates Cell Transformation, Tumorigenesis, and Invasion

2010 ◽  
Vol 30 (19) ◽  
pp. 4604-4615 ◽  
Author(s):  
Masahiro Tanji ◽  
Toshimasa Ishizaki ◽  
Saman Ebrahimi ◽  
Yuko Tsuboguchi ◽  
Taiko Sukezane ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Filaments ◽  
Focal Adhesions ◽  
Small Gtpase ◽  
Temperature Sensitive ◽  
Cell Periphery ◽  
Morphological Transformation ◽  
Focus Formation

ABSTRACT The small GTPase Rho regulates cell morphogenesis through remodeling of the actin cytoskeleton. While Rho is overexpressed in many clinical cancers, the role of Rho signaling in oncogenesis remains unknown. mDia1 is a Rho effector producing straight actin filaments. Here we transduced mouse embryonic fibroblasts from mDia1-deficient mice with temperature-sensitive v-Src and examined the involvement and mechanism of the Rho-mDia1 pathway in Src-induced oncogenesis. We showed that in v-Src-transduced mDia1-deficient cells, formation of actin filaments is suppressed, and v-Src in the perinuclear region does not move to focal adhesions upon a temperature shift. Consequently, membrane translocation of v-Src, v-Src-induced morphological transformation, and podosome formation are all suppressed in mDia1-deficient cells with impaired tyrosine phosphorylation. mDia1-deficient cells show reduced transformation in vitro as examined by focus formation and colony formation in soft agar and exhibit suppressed tumorigenesis and invasion when implanted in nude mice in vivo. Given overexpression of c-Src in various cancers, these findings suggest that Rho-mDia1 signaling facilitates malignant transformation and invasion by manipulating the actin cytoskeleton and targeting Src to the cell periphery.

scholarly journals Force-FAK Signaling Coupling at Individual Focal Adhesions Coordinates Mechanosensing and Microtissue Repair

2020 ◽  
Author(s):  
Dennis Zhou ◽  
Marc Fernández-Yagüe ◽  
Elijah Holland ◽  
Andrés García ◽  
Nicolas Castro ◽  
...  
Keyword(s):  
Cell Migration ◽  
Magnetic Beads ◽  
Focal Adhesions ◽  
Traction Force ◽  
Binding Model ◽  
Wound Healing Model ◽  
External Forces ◽  
Biochemical Signals ◽  
Healing Model

Abstract How adhesive forces are transduced and integrated into biochemical signals at focal adhesions (FAs) is poorly understood. Using cells adhering to deformable micropillar arrays, we demonstrate that traction force and FAK localization as well as traction force and Y397-FAK phosphorylation are linearly coupled at individual FAs on stiff, but not soft, substrates. Similarly, FAK phosphorylation increases linearly with external forces applied to FAs using magnetic beads. This mechanosignaling coupling requires actomyosin contractility, talin-FAK binding, and full-length vinculin that binds talin and actin. Using an in vitro 3D biomimetic wound healing model, we show that force-FAK signaling coupling coordinates cell migration and tissue-scale forces to promote microtissue repair. A simple kinetic binding model of talin-FAK interactions under force can recapitulate the experimental observations. This study provides insights on how talin and vinculin convert forces into FAK signaling events regulating cell migration and tissue repair.

scholarly journals Rho GTPases Control Polarity, Protrusion, and Adhesion during Cell Movement

1999 ◽  
Vol 144 (6) ◽  
pp. 1235-1244 ◽  
Author(s):  
Catherine D. Nobes ◽  
Alan Hall
Keyword(s):  
Rho Gtpases ◽  
Actin Filaments ◽  
Cell Movement ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Small Gtpases ◽  
Animal Cells ◽  
Forward Movement ◽  
Direction Of Movement

Cell movement is essential during embryogenesis to establish tissue patterns and to drive morphogenetic pathways and in the adult for tissue repair and to direct cells to sites of infection. Animal cells move by crawling and the driving force is derived primarily from the coordinated assembly and disassembly of actin filaments. The small GTPases, Rho, Rac, and Cdc42, regulate the organization of actin filaments and we have analyzed their contributions to the movement of primary embryo fibroblasts in an in vitro wound healing assay. Rac is essential for the protrusion of lamellipodia and for forward movement. Cdc42 is required to maintain cell polarity, which includes the localization of lamellipodial activity to the leading edge and the reorientation of the Golgi apparatus in the direction of movement. Rho is required to maintain cell adhesion during movement, but stress fibers and focal adhesions are not required. Finally, Ras regulates focal adhesion and stress fiber turnover and this is essential for cell movement. We conclude that the signal transduction pathways controlled by the four small GTPases, Rho, Rac, Cdc42, and Ras, cooperate to promote cell movement.

scholarly journals Force-FAK signaling coupling at individual focal adhesions coordinates mechanosensing and microtissue repair

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dennis W. Zhou ◽  
Marc A. Fernández-Yagüe ◽  
Elijah N. Holland ◽  
Andrés F. García ◽  
Nicolas S. Castro ◽  
...  
Keyword(s):  
Cell Migration ◽  
Magnetic Beads ◽  
Focal Adhesions ◽  
Traction Force ◽  
Binding Model ◽  
Wound Healing Model ◽  
External Forces ◽  
Biochemical Signals ◽  
Healing Model

AbstractHow adhesive forces are transduced and integrated into biochemical signals at focal adhesions (FAs) is poorly understood. Using cells adhering to deformable micropillar arrays, we demonstrate that traction force and FAK localization as well as traction force and Y397-FAK phosphorylation are linearly coupled at individual FAs on stiff, but not soft, substrates. Similarly, FAK phosphorylation increases linearly with external forces applied to FAs using magnetic beads. This mechanosignaling coupling requires actomyosin contractility, talin-FAK binding, and full-length vinculin that binds talin and actin. Using an in vitro 3D biomimetic wound healing model, we show that force-FAK signaling coupling coordinates cell migration and tissue-scale forces to promote microtissue repair. A simple kinetic binding model of talin-FAK interactions under force can recapitulate the experimental observations. This study provides insights on how talin and vinculin convert forces into FAK signaling events regulating cell migration and tissue repair.

The In Vitro Antibiofilm Activity of Water Leaf Extract of Papaya (Carica papaya L.) against Pseudomonas aeruginosa

2017 ◽  
Vol 2 (3) ◽  
pp. 150-163
Author(s):  
Ekajayanti Kining ◽  
Syamsul Falah ◽  
Novik Nurhidayat
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Contact Time ◽  
Cell Attachment ◽  
Water Extract ◽  
Opportunistic Pathogen ◽  
Bacterial Biofilm ◽  
Antibiofilm Activity ◽  
Bacterial Survival ◽  
Optimum Conditions

Pseudomonas aeruginosa is one of opportunistic pathogen forming bacterial biofilm. The biofilm sustains the bacterial survival and infections. This study aimed to assess the activity of water extract of papaya leaves on inhibition of cells attachment, growth and degradation of the biofilm using crystal violet (CV) biofilm assay. Research results showed that water extract of papaya leaves contains alkaloids, tanins, flavonoids, and steroids/terpenoids and showed antibacterial activity and antibiofilm against P. aeruginosa. Addition of extract can inhibit the cell attachment and was able to degrade the biofilm of 40.92% and 48.058% respectively at optimum conditions: extract concentration of 25% (v/v), temperature 37.5 °C and contact time 45 minutes. With a concentration of 25% (v/v), temperature of 50 °C and the contact time of 3 days, extract of papaya leaves can inhibit the growth of biofilms of 39.837% v/v.

scholarly journals Platelet Shape Changes during Thrombus Formation: Role of Actin-Based Protrusions

2021 ◽  
Vol 41 (01) ◽  
pp. 014-021
Author(s):  
Markus Bender ◽  
Raghavendra Palankar
Keyword(s):  
Blood Loss ◽  
Actin Filaments ◽  
Thrombus Formation ◽  
Short Review ◽  
Critical Component ◽  
Clot Retraction ◽  
Shape Changes ◽  
Platelet Shape

AbstractPlatelet activation and aggregation are essential to limit blood loss at sites of vascular injury but may also lead to occlusion of diseased vessels. The platelet cytoskeleton is a critical component for proper hemostatic function. Platelets change their shape after activation and their contractile machinery mediates thrombus stabilization and clot retraction. In vitro studies have shown that platelets, which come into contact with proteins such as fibrinogen, spread and first form filopodia and then lamellipodia, the latter being plate-like protrusions with branched actin filaments. However, the role of platelet lamellipodia in hemostasis and thrombus formation has been unclear until recently. This short review will briefly summarize the recent findings on the contribution of the actin cytoskeleton and lamellipodial structures to platelet function.

Myofibrillar degeneration with diphtheria toxin

2020 ◽  
Vol 45 (4) ◽  
pp. 351-357
Author(s):  
Bilge Özerman Edis ◽  
Muhammet Bektaş ◽  
Rüstem Nurten
Keyword(s):  
Protein Synthesis ◽  
Actin Filaments ◽  
Diphtheria Toxin ◽  
Cardiac Tissue ◽  
Culture Conditions ◽  
Bacterial Toxin ◽  
Filamentous Actin ◽  
Cardiac Damage ◽  
Tissue Samples

AbstractObjectivesCardiac damage in patient with diphtheritic myocarditis is reported as the leading cause of mortality. Diphtheria toxin (DTx) is a well-known bacterial toxin inducing various cytotoxic effects. Mainly, catalytic fragment inhibits protein synthesis, induces cytotoxicity, and depolymerizes actin filaments. In this study, we aimed to demonstrate the extent of myofibrillar damage under DTx treatment to porcine cardiac tissue samples.MethodsTissue samples were incubated with DTx for 1–3 h in culture conditions. To analyze whole toxin (both fragments) distribution, conjugation of DTx with FITC was performed. Measurements were carried out with fluorescence spectrophotometer before and after dialysis. Immunofluorescence microscopy was used to show localization of DTx-FITC (15 nM) on cardiac tissue incubated for 2 h. Ultrastructural characterization of cardiac tissue samples treated with DTx (15 or 150 nM) was performed with transmission electron microscopy.ResultsDTx exerts myofibrillar disorganization. Myofilament degeneration, mitochondrial damage, vacuolization, and abundant lipid droplets were determined with 150 nM of DTx treatment.ConclusionsThis finding is an addition to depolymerization of actin filaments as a result of the DTx-actin interactions in in vitro conditions, indicating that myofilament damage can occur with DTx directly besides protein synthesis inhibition. Ultrastructural results support the importance of filamentous actin degeneration at diphtheritic myocarditis.

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