scholarly journals The Actomyosin Cytoskeleton Drives Micron-Scale Membrane Remodeling In Vivo Via the Generation of Mechanical Forces to Balance Membrane Tension Gradients

BioEssays ◽  
2018 ◽  
Vol 40 (9) ◽  
pp. 1800032 ◽  
Author(s):  
Seham Ebrahim ◽  
Jian Liu ◽  
Roberto Weigert
Keyword(s):  
Mechanical Forces ◽  
Membrane Tension ◽  
Membrane Remodeling ◽  
Actomyosin Cytoskeleton

scholarly journals ENDOSOMAL MEMBRANE TENSION CONTROLS ESCRT-III-DEPENDENT INTRA-LUMENAL VESICLE FORMATION

2019 ◽  
Author(s):  
Vincent Mercier ◽  
Jorge Larios ◽  
Guillaume Molinard ◽  
Antoine Goujon ◽  
Stefan Matile ◽  
...  
Keyword(s):  
Vesicle Formation ◽  
Membrane Tension ◽  
Membrane Remodeling ◽  
Intracellular Traffic ◽  
Physiological Conditions ◽  
Endosomal Membrane ◽  
Endosome Trafficking ◽  
Endosomal Membranes

AbstractPlasma membrane tension strongly affects cell surface processes, such as migration, endocytosis and signalling. However, it is not known whether membrane tension of organelles regulates their functions, notably intracellular traffic. The ESCRT-III complex is the major membrane remodelling complex that drives Intra-Lumenal Vesicle (ILV) formation on endosomal membranes. Here, we made use of a new fluorescent membrane tension probe to show that ESCRT-III subunits are recruited onto endosomal membranes when membrane tension is reduced. We find that tension-dependent recruitment is associated with ESCRT-III polymerization and membrane deformation in vitro, and correlates with increased ILVs formation in ESCRT-III decorated endosomes in vivo. Finally, we find that endosomal membrane tension decreases when ILV formation is triggered by EGF under physiological conditions. These results indicate that membrane tension is a major regulator of ILV formation and of endosome trafficking, leading us to conclude that membrane tension can control organelle functions.One Sentence SummaryMembrane tension decrease facilitates membrane remodeling by ESCRT-III polymerization during intra-lumenal vesicle formation.

The Role of Mechanical Tension in Neurons

2010 ◽  
Vol 1274 ◽  
Author(s):  
Taher Saif ◽  
Jagannathan Rajagopalan ◽  
Alireza Tofangchi
Keyword(s):  
Mechanical Response ◽  
Mechanical Forces ◽  
Active Tension ◽  
Mechanical Tension ◽  
Deformation Response ◽  
Linear Force ◽  
Tension Regulation ◽  
Over Time

AbstractWe used high resolution micromechanical force sensors to study the in vivo mechanical response of embryonic Drosophila neurons. Our experiments show that Drosophila axons have a rest tension of a few nN and respond to mechanical forces in a manner characteristic of viscoelastic solids. In response to fast externally applied stretch they show a linear force-deformation response and when the applied stretch is held constant the force in the axons relaxes to a steady state value over time. More importantly, when the tension in the axons is suddenly reduced by releasing the external force the neurons actively restore the tension, sometimes close to their resting value. Along with the recent findings of Siechen et al (Proc. Natl. Acad. Sci. USA 106, 12611 (2009)) showing a link between mechanical tension and synaptic plasticity, our observation of active tension regulation in neurons suggest an important role for mechanical forces in the functioning of neurons in vivo.

scholarly journals Self-organized cytoskeletal alignment during Drosophila mesoderm invagination

2020 ◽  
Vol 375 (1809) ◽  
pp. 20190551 ◽  
Author(s):  
Adam C. Martin
Keyword(s):  
Self Organization ◽  
Mechanical Forces ◽  
Feedback Process ◽  
Wild Type ◽  
Tissue Morphogenesis ◽  
Cell Behaviour ◽  
Feedback Mechanisms ◽  
Self Organized ◽  
Actomyosin Cytoskeleton ◽  
Shape Changes

During tissue morphogenesis, mechanical forces are propagated across tissues, resulting in tissue shape changes. These forces in turn can influence cell behaviour, leading to a feedback process that can be described as self-organizing. Here, I discuss cytoskeletal self-organization and point to evidence that suggests its role in directing force during morphogenesis. During Drosophila mesoderm invagination, the shape of the region of cells that initiates constriction creates a mechanical pattern that in turn aligns the cytoskeleton with the axis of greatest resistance to contraction. The wild-type direction of the force controls the shape and orientation of the invaginating mesoderm. Given the ability of the actomyosin cytoskeleton to self-organize, these types of feedback mechanisms are likely to play important roles in a range of different morphogenetic events. This article is part of the discussion meeting issue ‘Contemporary morphogenesis'.

scholarly journals A small proportion of Talin molecules transmit forces to achieve muscle attachment in vivo

2018 ◽  
Author(s):  
Sandra B. Lemke ◽  
Thomas Weidemann ◽  
Anna-Lena Cost ◽  
Carsten Grashoff ◽  
Frank Schnorrer
Keyword(s):  
Tissue Mechanics ◽  
Correlation Spectroscopy ◽  
Mechanical Forces ◽  
Muscle Attachment ◽  
Cell Fate Decisions ◽  
Mammalian Cell Lines ◽  
Attachment Sites ◽  
Molecular Forces ◽  
Muscle Attachment Sites

Cells in a developing organism are subjected to particular mechanical forces, which shape tissues and instruct cell fate decisions. How these forces are sensed and transmitted at the molecular level is thus an important question, which has mainly been investigated in cultured cells in vitro. Here, we elucidate how mechanical forces are transmitted in an intact organism. We studied Drosophila muscle attachment sites, which experience high mechanical forces during development and require integrin-mediated adhesion for stable attachment to tendons. Hence, we quantified molecular forces across the essential integrin-binding protein Talin, which links integrin to the actin cytoskeleton. Generating flies expressing three FRET-based Talin tension sensors reporting different force levels between 1 and 11 pN enabled us to quantify physiologically-relevant, molecular forces. By measuring primary Drosophila muscle cells, we demonstrate that Drosophila Talin experiences mechanical forces in cell culture that are similar to those previously reported for Talin in mammalian cell lines. However, in vivo force measurements at developing flight muscle attachment sites revealed that average forces across Talin are comparatively low and decrease even further while attachments mature and tissue-level tension increases. Concomitantly, Talin concentration at attachment sites increases five-fold as quantified by fluorescence correlation spectroscopy, suggesting that only few Talin molecules are mechanically engaged at any given time. We therefore propose that high tissue forces are shared amongst a large excess of adhesion molecules of which less than 15% are experiencing detectable forces at the same time. Our findings define an important new concept of how cells can adapt to changes in tissue mechanics to prevent mechanical failure in vivo.

Pathological shear stress directly regulates platelet αIIbβ3signaling

2006 ◽  
Vol 291 (6) ◽  
pp. C1346-C1354 ◽  
Author(s):  
Shuju Feng ◽  
Xin Lu ◽  
Julio C. Reséndiz ◽  
Michael H. Kroll
Keyword(s):  
Shear Stress ◽  
Ligand Binding ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Tyrosine Kinases ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Human Platelets ◽  
Mechanical Forces

Integrin mechanotransduction is a ubiquitous biological process. Mechanical forces are transduced transmembranously by an integrin's ligand-bound extracellular domain through its β-subunit's cytoplasmic domain connected to the cytoskeleton. This often culminates in the activation of tyrosine kinases directing cell responses. The delicate balance between hemostasis and thrombosis requires exquisitely fine-tuned integrin function, and balance is maintained in vivo despite that the major platelet integrin αIIbβ3is continuously subjected to frictional or shearing forces generated by laminar blood flow. To test the hypothesis that platelet function is regulated by the direct effects of mechanical forces on αIIbβ3, we examined αIIbβ3/cytoskeletal interactions in human platelets exposed to shear stress in a cone-plate viscometer. We observed that α-actinin, myosin heavy chain, and Syk coimmunoprecipitate with αIIbβ3in resting platelets and that 120 dyn/cm2shear stress leads to their disassociation from αIIbβ3. Shear-induced disassociation of α-actinin and myosin heavy chain from the β3tail is unaffected by blocking von Willebrand factor (VWF) binding to glycoprotein (Gp) Ib-IX-V but abolished by blocking VWF binding to αIIbβ3. Syk's disassociation from β3is inhibited when VWF binding to either GpIb-IX-V or αIIbβ3is blocked. Shear stress-induced phosphorylation of SLP-76 and its association with tyrosine-phosphorylated adhesion and degranulation-promoting adapter protein are inhibited by blocking ligand binding to αIIbβ3but not by blocking ligand binding to GpIb-IX-V. Chinese hamster ovary cells expressing αIIbβ3with β3truncated of its cytoskeletal binding domains demonstrate diminished shear-dependent adhesion and cohesion. These results support the hypothesis that shear stress directly modulates αIIbβ3function and suggest that shear-induced αIIbβ3-mediated signaling contributes to the regulation of platelet aggregation by directing the release of constraining cytoskeletal elements from the β3-tail.

scholarly journals Droplet Based Measurements of Mechanical Forces and Material Properties, In Vivo and In Vitro

2018 ◽  
Vol 114 (3) ◽  
pp. 666a
Author(s):  
Elijah Shelton ◽  
Adam Lucio ◽  
Hannah Gustafson ◽  
Alessandro Mongera ◽  
Friedhelm Serwane ◽  
...  
Keyword(s):  
Material Properties ◽  
Mechanical Forces

Force-dependent vinculin binding to talin in live cells: a crucial step in anchoring the actin cytoskeleton to focal adhesions

2014 ◽  
Vol 306 (6) ◽  
pp. C607-C620 ◽  
Author(s):  
Hiroaki Hirata ◽  
Hitoshi Tatsumi ◽  
Chwee Teck Lim ◽  
Masahiro Sokabe
Keyword(s):  
Actin Cytoskeleton ◽  
Focal Adhesions ◽  
Living Cells ◽  
Live Cells ◽  
Mechanical Forces ◽  
Actin Network ◽  
Crucial Step

Mechanical forces play a pivotal role in the regulation of focal adhesions (FAs) where the actin cytoskeleton is anchored to the extracellular matrix through integrin and a variety of linker proteins including talin and vinculin. The localization of vinculin at FAs depends on mechanical forces. While in vitro studies have demonstrated the force-induced increase in vinculin binding to talin, it remains unclear whether such a mechanism exists at FAs in vivo. In this study, using fibroblasts cultured on elastic silicone substrata, we have examined the role of forces in modulating talin-vinculin binding at FAs. Stretching the substrata caused vinculin accumulation at talin-containing FAs, and this accumulation was abrogated by expressing the talin-binding domain of vinculin (domain D1, which inhibits endogenous vinculin from binding to talin). These results indicate that mechanical forces loaded to FAs facilitate vinculin binding to talin at FAs. In cell-protruding regions, the actin network moved backward over talin-containing FAs in domain D1-expressing cells while it was anchored to FAs in control cells, suggesting that the force-dependent vinculin binding to talin is crucial for anchoring the actin cytoskeleton to FAs in living cells.

Dynamics of Human Coronary Arterial Motion and Its Potential Role in Coronary Atherogenesis

2000 ◽  
Vol 122 (5) ◽  
pp. 488-492 ◽  
Author(s):  
Zhaohua Ding ◽  
Morton H. Friedman
Keyword(s):  
Coronary Arteries ◽  
Potential Role ◽  
Fluid Dynamic ◽  
Mechanical Forces ◽  
Motion Patterns ◽  
Coefficients Of Variation ◽  
Motion Parameters ◽  
Arterial Motion ◽  
Vessel Axis

Mechanical forces have been widely recognized to play an important role in the pathogenesis of atherosclerosis. Since coronary arterial motion modulates both vessel wall mechanics and fluid dynamics, it is hypothesized that certain motion patterns might be atherogenic by generating adverse wall mechanical forces or fluid dynamic environments. To characterize the dynamics of coronary arterial motion and explore its implications in atherogenesis, a system was developed to track the motion of coronary arteries in vivo, and employed to quantify the dynamics of four right coronary arteries (RCA) and eight left anterior descending (LAD) coronary arteries. The analysis shows that: (a) The motion parameters vary among individuals, with coefficients of variation ranging from 0.25 to 0.59 for axially and temporally averaged values of the parameters; (b) the motion parameters of individual vessels vary widely along the vessel axis, with coefficients of variation as high as 2.28; (c) the LAD exhibits a greater axial variability in torsion, a measure of curve “helicity,” than the RCA; (d) in comparison with the RCA, the LAD experiences less displacement p=0.009, but higher torsion p=0.03. These results suggest that: (i) the variability of certain motion parameters, particularly those that exhibit large axial variations, might be related to variations in susceptibility to atherosclerosis among different individuals and vascular regions; and (ii) differences in motion parameters between the RCA and LAD might relate to differences in their susceptibility to atherosclerosis. [S0148-0731(00)00405-2]

scholarly journals Growth factors are released by mechanically wounded endothelial cells.

1989 ◽  
Vol 109 (2) ◽  
pp. 811-822 ◽  
Author(s):  
P L McNeil ◽  
L Muthukrishnan ◽  
E Warder ◽  
P A D'Amore
Keyword(s):  
Endothelial Cells ◽  
Plasma Membrane ◽  
Growth Factors ◽  
Growth Factor ◽  
Mechanical Forces ◽  
Fibroblast Growth ◽  
Growth Promoting ◽  
Transient Plasma

Growth factors may be required at sites of mechanical injury and normal wear and tear in vivo, suggesting that the direct action of mechanical forces on cells could lead to growth factor release. Scraping of cells from the tissue culture substratum at 37 degrees C was used to test this possibility. We show that scraping closely mimics in vitro both the transient plasma membrane wounds observed in cells subject to mechanical forces in vivo (McNeil, P. L., and S. Ito. 1989. Gastroenterology. 96:1238-1248) and the transient plasma membrane wounds shown here to occur in endothelial cells under normal culturing conditions. Scraping of endothelial cells from the culturing substratum released into the culture medium a potent growth-promoting activity for Swiss 3T3 fibroblasts. Growth-promoting activity was released rapidly (within 5 min) after scraping but was not subsequently degraded by the endothelial cells for at least 24 h thereafter. A greater quantity of growth-promoting activity was released by cells scraped 4 h after plating than by those scraped 4 or 7 d afterwards. Thus release is not due to scraping-induced disruption of extracellular matrix. Release was only partially cold inhibitable, was poorly correlated with the level of cell death induced by scraping, and did not occur when cells were killed with metabolic poisons. These results suggest that mechanical disruption of plasma membrane, either transient or permanent, is the essential event leading to release. A basic fibroblast growth factor-like molecule and not platelet-derived growth factor appears to be partially responsible for the growth-promoting activity. We conclude that one biologically relevant route of release of basic fibroblast growth factor, a molecule which lacks the signal peptide sequence for transport into the endoplasmic reticulum, could be directly through mechanically induced membrane disruptions of endothelial cells growing in vivo and in vitro.

Integrin signaling's potential for mediating gene expression in hypertrophying skeletal muscle

2000 ◽  
Vol 88 (1) ◽  
pp. 337-343 ◽  
Author(s):  
James A. Carson ◽  
Lei Wei
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Mechanical Load ◽  
Integrin Signaling ◽  
Mechanical Forces ◽  
Growth Factor Signaling ◽  
Muscle Gene

Overloaded skeletal muscle undergoes dramatic shifts in gene expression, which alter both the phenotype and mass. Molecular biology techniques employing both in vivo and in vitro hypertrophy models have demonstrated that mechanical forces can alter skeletal muscle gene regulation. This review's purpose is to support integrin-mediated signaling as a candidate for mechanical load-induced hypertrophy. Research quantifying components of the integrin-signaling pathway in overloaded skeletal muscle have been integrated with knowledge regarding integrins role during development and cardiac hypertrophy, with the hope of demonstrating the pathway's importance. The role of integrin signaling as an integrator of mechanical forces and growth factor signaling during hypertrophy is discussed. Specific components of integrin signaling, including focal adhesion kinase and low-molecular-weight GTPase Rho are mentioned as downstream targets of this signaling pathway. There is a need for additional mechanistic studies capable of providing a stronger linkage between integrin-mediated signaling and skeletal muscle hypertrophy; however, there appears to be abundant justification for this type of research.

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