Efficiency of collective myosin II motors studied with an elastic coupling power-stroke ratchet model

2018 ◽  
Vol 27 (12) ◽  
pp. 128701
Author(s):  
Zi-Qing Wang ◽  
Jin-Fang Li ◽  
Ying-Ge Xie ◽  
Guo-Dong Wang ◽  
Yao-Gen Shu
Keyword(s):  
Myosin Ii ◽  
Power Stroke ◽  
Elastic Coupling ◽  
Ratchet Model

scholarly journals Pharmacological activation of myosin II paralogs to correct cell mechanics defects

2015 ◽  
Vol 112 (5) ◽  
pp. 1428-1433 ◽  
Author(s):  
Alexandra Surcel ◽  
Win Pin Ng ◽  
Hoku West-Foyle ◽  
Qingfeng Zhu ◽  
Yixin Ren ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Mechanics ◽  
Myosin Ii ◽  
Target Space ◽  
Power Stroke ◽  
Invasion And Migration ◽  
Cortical Tension ◽  
Pancreatic Cancer Cells ◽  
Tumor Cell Behavior ◽  
And Migration

Current approaches to cancer treatment focus on targeting signal transduction pathways. Here, we develop an alternative system for targeting cell mechanics for the discovery of novel therapeutics. We designed a live-cell, high-throughput chemical screen to identify mechanical modulators. We characterized 4-hydroxyacetophenone (4-HAP), which enhances the cortical localization of the mechanoenzyme myosin II, independent of myosin heavy-chain phosphorylation, thus increasing cellular cortical tension. To shift cell mechanics, 4-HAP requires myosin II, including its full power stroke, specifically activating human myosin IIB (MYH10) and human myosin IIC (MYH14), but not human myosin IIA (MYH9). We further demonstrated that invasive pancreatic cancer cells are more deformable than normal pancreatic ductal epithelial cells, a mechanical profile that was partially corrected with 4-HAP, which also decreased the invasion and migration of these cancer cells. Overall, 4-HAP modifies nonmuscle myosin II-based cell mechanics across phylogeny and disease states and provides proof of concept that cell mechanics offer a rich drug target space, allowing for possible corrective modulation of tumor cell behavior.

Millisecond Conformational Dynamics of Skeletal Myosin II Power Stroke Studied by High-Speed Atomic Force Microscopy

ACS Nano ◽  
2020 ◽  
Author(s):  
Oleg S. Matusovsky ◽  
Noriyuki Kodera ◽  
Caitlin MacEachen ◽  
Toshio Ando ◽  
Yu-Shu Cheng ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
High Speed ◽  
Myosin Ii ◽  
Conformational Dynamics ◽  
Power Stroke ◽  
Force Microscopy ◽  
Atomic Force ◽  
Skeletal Myosin

scholarly journals Evolution of mechanical cooperativity among myosin II motors

2021 ◽  
Vol 118 (20) ◽  
pp. e2101871118
Author(s):  
Jason A. Wagoner ◽  
Ken A. Dill
Keyword(s):  
Collective Action ◽  
Muscle Contraction ◽  
External Load ◽  
Myosin Ii ◽  
Power Stroke ◽  
Biological Functions ◽  
Trade Off ◽  
Muscle Tissues ◽  
Motor Actions ◽  
Individual Motor

Myosin II is a biomolecular machine that is responsible for muscle contraction. Myosin II motors act cooperatively: during muscle contraction, multiple motors bind to a single actin filament and pull it against an external load, like people pulling on a rope in a tug-of-war. We model the dynamics of actomyosin filaments in order to study the evolution of motor–motor cooperativity. We find that filament backsliding—the distance an actin slides backward when a motor at the end of its cycle releases—is central to the speed and efficiency of muscle contraction. Our model predicts that this backsliding has been reduced through evolutionary adaptations to the motor’s binding propensity, the strength of the motor’s power stroke, and the force dependence of the motor’s release from actin. These properties optimize the collective action of myosin II motors, which is not a simple sum of individual motor actions. The model also shows that these evolutionary variables can explain the speed–efficiency trade-off observed across different muscle tissues. This is an example of how evolution can tune the microscopic properties of individual proteins in order to optimize complex biological functions.

scholarly journals Elastic coupling power stroke mechanism of the F1-ATPase molecular motor

2018 ◽  
Vol 115 (22) ◽  
pp. 5750-5755 ◽  
Author(s):  
James L. Martin ◽  
Robert Ishmukhametov ◽  
David Spetzler ◽  
Tassilo Hornung ◽  
Wayne D. Frasch
Keyword(s):  
Equilibrium Position ◽  
Phase 1 ◽  
Catalytic Site ◽  
Power Stroke ◽  
Atp Binding ◽  
Elastic Coupling ◽  
Phase 2 ◽  
Additional Energy ◽  
Torsion Spring ◽  
Γ Subunit

The angular velocity profile of the 120° F1-ATPase power stroke was resolved as a function of temperature from 16.3 to 44.6 °C using a ΔμATP = −31.25 kBT at a time resolution of 10 μs. Angular velocities during the first 60° of the power stroke (phase 1) varied inversely with temperature, resulting in negative activation energies with a parabolic dependence. This is direct evidence that phase 1 rotation derives from elastic energy (spring constant, κ = 50 kBT·rad−2). Phase 2 of the power stroke had an enthalpic component indicating that additional energy input occurred to enable the γ-subunit to overcome energy stored by the spring after rotating beyond its 34° equilibrium position. The correlation between the probability distribution of ATP binding to the empty catalytic site and the negative Ea values of the power stroke during phase 1 suggests that this additional energy is derived from the binding of ATP to the empty catalytic site. A second torsion spring (κ = 150 kBT·rad−2; equilibrium position, 90°) was also evident that mitigated the enthalpic cost of phase 2 rotation. The maximum ΔGǂ was 22.6 kBT, and maximum efficiency was 72%. An elastic coupling mechanism is proposed that uses the coiled-coil domain of the γ-subunit rotor as a torsion spring during phase 1, and then as a crankshaft driven by ATP-binding–dependent conformational changes during phase 2 to drive the power stroke.

Mechanics of the power stroke in myosin II

2010 ◽  
Vol 81 (5) ◽  
Author(s):  
L. Marcucci ◽  
L. Truskinovsky
Keyword(s):  
Myosin Ii ◽  
Power Stroke

Ciliary coordination in newt lung cells requires microtubule-based linkages between basal bodies: A correlative light and EM study

1992 ◽  
Vol 50 (1) ◽  
pp. 570-571
Author(s):  
Robert Hard ◽  
Gerald Rupp ◽  
Matthew L. Withiam-Leitch ◽  
Lisa Cardamone
Keyword(s):  
Basal Body ◽  
Untreated Control ◽  
Beat Frequency ◽  
Primary Cultures ◽  
Living Cells ◽  
Power Stroke ◽  
Ultrastructural Changes ◽  
Lung Cells ◽  
Basal Bodies ◽  
Ciliated Cells

In a coordinated field of beating cilia, the direction of the power stroke is correlated with the orientation of basal body appendages, called basal feet. In newt lung ciliated cells, adjacent basal feet are interconnected by cold-stable microtubules (basal MTs). In the present study, we investigate the hypothesis that these basal MTs stabilize ciliary distribution and alignment. To accomplish this, newt lung primary cultures were treated with the microtubule disrupting agent, Colcemid. In newt lung cultures, cilia normally disperse in a characteristic fashion as the mucociliary epithelium migrates from the tissue explant. Four arbitrary, but progressive stages of dispersion were defined and used to monitor this redistribution process. Ciliaiy beat frequency, coordination, and dispersion were assessed for 91 hrs in untreated (control) and treated cultures. When compared to controls, cilia dispersed more rapidly and ciliary coordination decreased markedly in cultures treated with Colcemid (2 mM). Correlative LM/EM was used to assess whether these effects of Colcemid were coupled to ultrastructural changes. Living cells were defined as having coordinated or uncoordinated cilia and then were processed for transmission EM.

Magnesium Chloride is an Effective Therapeutic Agent for Prostate Cancer

2018 ◽  
Vol 8 (1) ◽  
pp. 62 ◽  
Author(s):  
Julianna Maria Santos ◽  
Fazle Hussain
Keyword(s):  
Prostate Cancer ◽  
Magnesium Chloride ◽  
Epithelial Mesenchymal Transition ◽  
Chromatin Condensation ◽  
Myosin Ii ◽  
In Vivo Studies ◽  
Migration Speed ◽  
Mesenchymal Transition

Background: Reduced levels of magnesium can cause several diseases and increase cancer risk. Motivated by magnesium chloride’s (MgCl2) non-toxicity, physiological importance, and beneficial clinical applications, we studied its action mechanism and possible mechanical, molecular, and physiological effects in prostate cancer with different metastatic potentials.Methods: We examined the effects of MgCl2, after 24 and 48 hours, on apoptosis, cell migration, expression of epithelial mesenchymal transition (EMT) markers, and V-H+-ATPase, myosin II (NMII) and the transcription factor NF Kappa B (NFkB) expressions.Results: MgCl2 induces apoptosis, and significantly decreases migration speed in cancer cells with different metastatic potentials.  MgCl2 reduces the expression of V-H+-ATPase and myosin II that facilitates invasion and metastasis, suppresses the expression of vimentin and increases expression of E-cadherin, suggesting a role of MgCl2 in reversing the EMT. MgCl2 also significantly increases the chromatin condensation and decreases NFkB expression.Conclusions: These results suggest a promising preventive and therapeutic role of MgCl2 for prostate cancer. Further studies should explore extending MgCl2 therapy to in vivo studies and other cancer types.Keywords: Magnesium chloride, prostate cancer, migration speed, V-H+-ATPase, and EMT.

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