Mechanics and energetics of myosin molecular motors from nonpregnant human myometrium

2011 ◽  
Vol 111 (4) ◽  
pp. 1096-1105 ◽  
Author(s):  
Edouard R. Lecarpentier ◽  
Victor A. Claes ◽  
Oumar Timbely ◽  
Abdelilah Arsalane ◽  
Jacques A. Wipff ◽  
...  

Mechanical properties of spontaneously contracting isolated nonpregnant human myometrium (NPHM) were investigated throughout the whole continuum of load from zero load up to isometry. This made it possible to assess the three-dimensional tension-velocity-length (T-V-L) relationship characterizing the level of contractility and to determine crossbridge (CB) kinetics of myosin molecular motors. Seventy-seven muscle strips were obtained from hysterectomy in 42 nonpregnant patients. Contraction and relaxation parameters were measured during spontaneous mechanical activity. The isotonic tension-peak velocity (T-V) relationship was hyperbolic in 30 cases and nonhyperbolic in 47 cases. When the T-V relationship was hyperbolic, the Huxley formalism could be used to calculate CB kinetics and CB unitary force. At the whole muscle level and for a given isotonic load level, part of the V-L phase plane showed a common pathway, so that a given instantaneous length corresponded to only one possible instantaneous velocity, independent of time and initial length. At the molecular level, rate constants for CB attachment and detachment were dramatically low, ∼100 times lower than those of striated muscles, and ∼5 to 10 times lower than those of other smooth muscles. The CB unitary force was ∼1.4 ± 0.1 pN. NPHM shared similar basic contractile properties with striated muscles, reflected in the three-dimensional T-V-L relationship characterizing the contractile level. Low CB attachment and detachment rate constants made it possible to generate normal CB unitary force and normal muscle tension in NPHM, even though it contracted extremely slowly compared with other muscles.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Satoru Muro ◽  
Janyaruk Suriyut ◽  
Keiichi Akita

AbstractThis study presents the detailed anatomy of the Cowper’s gland in humans. Elucidating the mechanism of secretion and emission of the Cowper’s gland requires analysis of the muscles around the Cowper’s gland. We hypothesized that the Cowper’s gland involves not only smooth muscle but also the striated muscles of the pelvic floor. Here, we provide comprehensive and three-dimensional anatomy of the Cowper’s gland and its surrounding structures, which overcomes the current local and planar understanding. In this study, seven male corpses of body donors were used to conduct macroscopic anatomy, histology, and three-dimensional reconstruction. The Cowper’s gland was surrounded laterally and posterosuperiorly by striated and smooth muscles, respectively. The striated muscle bundle was connected from the superficial transverse perineal muscle, levator ani, and external anal sphincter to the external urethral sphincter (rhabdosphincter). The smooth muscle was part of the deep transverse perineal muscle and entered between the bilateral Cowper’s glands and lobules. Our findings indicate that the secretion and emission of the Cowper’s gland in humans are carried out through the cooperation of striated and smooth muscles.


2002 ◽  
Vol 30 (2) ◽  
pp. 285-290 ◽  
Author(s):  
G. Goldspink

Muscle has an intrinsic ability to change its mass and phenotype in response to activity. This process involves quantitative and qualitative changes in gene expression, including that of the myosin heavy chain isogenes that encode different types of molecular motors. This, and the differential expression of metabolic genes, results in altered fatigue resistance and power output. The regulation of muscle mass involves autocrine as well as systemic factors. We have cloned the cDNAs of local and systemic isoforms of insulin-like growth factor-I (IGF-I) from exercised muscle. Although different isoforms are derived from the IGF-I gene by alternative splicing, the RNA transcript of one of them is only detectable following injury and/or mechanical activity. Thus this protein has been called mechano growth factor (MGF). Because of a reading-frame shift, MGF has a different 3′ sequence and a different mode of action compared with systemic or liver IGF-I. Although MGF has been called a growth factor, it may be regulated as a local repair factor.


2011 ◽  
Vol 65 (1-2) ◽  
pp. 51-59 ◽  
Author(s):  
Indira Mujezinovic ◽  
Vitomir Cupic ◽  
Ahmed Smajlovic ◽  
Mehmed Muminovic

Serotonin or 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter synthesised from L-tryptophan in serotonergic neurons and enterochromaffin cells of the gastrointestinal tract. This neurotransmitter is widely distributed in the animal and plant kingdom and regulates some central and peripheral functions through several types of specific serotonergic (5-HT) receptors. Since it is known that the effect of serotonin, especially in pathological conditions, is very important, we believe that determining the types of receptors for this substance would make it possible to use their agonist or antagonists, which would undoubtedly enhance the pharmacotherapy of functional disruption of the small intestine in broilers. Investigations were carried out on isolated smooth muscle strips of the circular and longitudinal layer of the broiler small intestine (strip dimension 3-4 mm x 2 cm). The muscle strips were placed in an isolated organ bath. The mechanical activity of the preparations was recorded via an isotonic force transducer coupled to a pen recorder. This was done following the addition of serotonin (nonselective 5-HT agonist), 8-OH-DPAT (selective 5-HT1A agonist) and spiroxatrin (selective 5-HT1A antagonist). The sensitivity of the tissues to acetylcholine was tested before starting the experiments. Using the obtained results, it can be concluded that 5HT1A type receptors are present in smooth muscles of the broiler small intestine, duodenum and ileum, especially in the longitudinal smooth muscle layer which reacted with contractions even to low serotonin concentration (10-6), but not in the jejunum.


1967 ◽  
Vol 47 (2) ◽  
pp. 249-265
Author(s):  
M. E. J. HOLWILL ◽  
N. R. SILVESTER

1. The frequencies of the beat of cilia and flagella from various organisms have been determined at temperatures in the range 5-35°C. 2. Values of the activation enthalpy (ΔH‡, kcal./mole) and activation entropy (ΔS‡, e.u.) derived from the thermal dependence of frequency show a linear correlation of the form, ΔS‡ = 3·25 ΔH‡-50·75. 3. The corresponding isokinetic activation free energy is 15·6 kcal./mole. 4. The results support a hypothesis that the breakdown of an ATP-ATPase complex could be the common rate-limiting reaction for flagellar activity. 5. Values of ΔH‡ and ΔS‡ for the decay of length or tension in striated muscles also fall on the same regression line but some smooth muscles show deviations.


2019 ◽  
Author(s):  
Edgar Uhl ◽  
Peter Mayer ◽  
Henry Dube

Light driven molecular motors possess immense potential as central driving units for future nanotechnology. Integration into larger molecular setups and transduction of their mechanical motions represents the current frontier of research. Here we report on an integrated molecular machine setup allowing to transmit potential energy from a motor unit unto a remote receiving entity. The setup consists of a motor unit connected covalently to a distant and sterically strongly encumbered biaryl receiver. By action of the motor unit single bond rotation of the receiver is strongly accelerated and forced to proceed unidirectionally. The transmitted potential energy is directly measured as the extent to which energy degeneration is lifted in the thermal atropisomerization of this biaryl. Energy degeneracy is reduced by as much as 2.3 kcal/mol and rate accelerations up to 2x10<sup>5</sup> fold in terms of rate constants are achieved.<br><b></b>


1985 ◽  
Vol 100 (6) ◽  
pp. 2025-2030 ◽  
Author(s):  
H Takano-Ohmuro ◽  
T Obinata ◽  
M Kawashima ◽  
T Masaki ◽  
T Tanaka

It has been demonstrated that embryonic chicken gizzard smooth muscle contains a unique embryonic myosin light chain of 23,000 mol wt, called L23 (Katoh, N., and S. Kubo, 1978, Biochem. Biophys. Acta, 535:401-411; Takano-Ohmuro, H., T. Obinata, T. Mikawa, and T. Masaki, 1983, J. Biochem. (Tokyo), 93:903-908). When we examined myosins in developing chicken ventricular and pectoralis muscles by two-dimensional gel electrophoresis, the myosin light chain (Le) that completely comigrates with L23 was detected in both striated muscles at early developmental stages. Two monoclonal antibodies, MT-53f and MT-185d, were applied to characterize the embryonic light chain Le of striated muscles. Both monoclonal antibodies were raised to fast skeletal muscle myosin light chains; the former antibody is specific to fast muscle myosin light chains 1 and 3, whereas the latter recognizes not only fast muscle myosin light chains but also the embryonic smooth muscle light chain L23. The immunoblots combined with both one- and two-dimensional gel electrophoresis showed that Le reacts with MT-185d but not with MT-53f. These results strongly indicate that Le is identical to L23 and that embryonic chicken skeletal, cardiac, and smooth muscles express a common embryo-specific myosin light chain.


2020 ◽  
Vol 142 (5) ◽  
Author(s):  
Dean Culver ◽  
Bryan Glaz ◽  
Samuel Stanton

Abstract Animal skeletal muscle exhibits very interesting behavior at near-stall forces (when the muscle is loaded so strongly that it can barely contract). Near this physical limit, the myosin II proteins may be unable to reach advantageous actin binding sites through simple attractive forces. It has been shown that the advantageous utilization of thermal agitation is a likely source for an increased force-production capacity and reach in myosin-V (a processing motor protein), and here we explore the dynamics of a molecular motor without hand-over-hand motion including Brownian motion to show how local elastic energy well boundaries may be overcome. We revisit a spatially two-dimensional mechanical model to illustrate how thermal agitation can be harvested for useful mechanical work in molecular machinery inspired by this biomechanical phenomenon without rate functions or empirically inspired spatial potential functions. Additionally, the model accommodates variable lattice spacing, and it paves the way for a full three-dimensional model of cross-bridge interactions where myosin II may be azimuthally misaligned with actin binding sites. With potential energy sources based entirely on realizable components, this model lends itself to the design of artificial, molecular-scale motors.


Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 287 ◽  
Author(s):  
Si-Kao Guo ◽  
Wei-Chi Wang ◽  
Peng-Ye Wang ◽  
Ping Xie

Kinesin-1, kinesin-2 and kinesin-5 are three families of a superfamily of motor proteins; which can walk processively on microtubule filaments by hydrolyzing ATP. It was experimentally shown that while the three kinesin dimers show similar feature on the force dependence of velocity, they show rather different features on the force dependence of run length. However, why the three families of kinesins show these rather different features is unclear. Here, we computationally studied the movement dynamics of the three dimers based on our proposed model. The simulated results reproduce well the available experimental data on the force dependence of velocity and run length. Moreover, the simulated results on the velocity and run length for the three dimers with altered neck linker lengths are also in quantitative agreement with the available experimental data. The studies indicate that the three families of kinesins show much similar movement mechanism and the rather different features on the force dependence of run length arise mainly from the difference in rate constants of the ATPase activity and neck linker docking. Additionally, the asymmetric (limping) movement dynamics of the three families of homodimers with and without altered neck linker lengths are studied, providing predicted results.


2019 ◽  
Vol 20 (19) ◽  
pp. 4911 ◽  
Author(s):  
Xie ◽  
Guo ◽  
Chen

A general kinetic model is presented for the chemomechanical coupling of dimeric kinesin molecular motors with and without extension of their neck linkers (NLs). A peculiar feature of the model is that the rate constants of ATPase activity of a kinesin head are independent of the strain on its NL, implying that the heads of the wild-type kinesin dimer and the mutant with extension of its NLs have the same force-independent rate constants of the ATPase activity. Based on the model, an analytical theory is presented on the force dependence of the dynamics of kinesin dimers with and without extension of their NLs at saturating ATP. With only a few adjustable parameters, diverse available single molecule data on the dynamics of various kinesin dimers, such as wild-type kinesin-1, kinesin-1 with mutated residues in the NLs, kinesin-1 with extension of the NLs and wild-type kinesin-2, under varying force and ATP concentration, can be reproduced very well. Additionally, we compare the power production among different kinesin dimers, showing that the mutation in the NLs reduces the power production and the extension of the NLs further reduces the power production.


Materials ◽  
2020 ◽  
Vol 13 (6) ◽  
pp. 1392
Author(s):  
Sebastian Jaeger ◽  
Maximilian Uhler ◽  
Stefan Schroeder ◽  
Nicholas A. Beckmann ◽  
Steffen Braun

The resulting inflammatory reaction to polyethylene (PE) wear debris, which may result in osteolysis, is still considered to be a main reason for aseptic loosening. In addition to the primary wear in hip joint replacements caused by head-insert articulation, relative motions between the PE liner and the metal cup may cause additional wear. In order to limit this motion, various locking mechanisms were used. We investigated three different locking mechanisms (Aesculap, DePuy, and Zimmer Biomet) to address the resulting relative motion between the acetabular cup and PE liner and the maximum disassembly force. A standardized setting with increasing load levels was used in combination with optically based three-dimensional measurements. In addition the maximum disassembly forces were evaluated according to the ASTM F1820-13 standard. Our data showed significant differences between the groups, with a maximum relative motion at the maximum load level (3.5 kN) of 86.5 ± 32.7 µm. The maximum axial disassembly force was 473.8 ± 94.6 N. The in vitro study showed that various locking mechanisms may influence cup-inlay stability.


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