scholarly journals Investigating the correlation of muscle function tests and sarcomere organization in C. elegans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leila Lesanpezeshki ◽  
Hiroshi Qadota ◽  
Masoud Norouzi Darabad ◽  
Karishma Kashyap ◽  
Carla M. R. Lacerda ◽  
...  

Abstract Background Caenorhabditis elegans has been widely used as a model to study muscle structure and function. Its body wall muscle is functionally and structurally similar to vertebrate skeletal muscle with conserved molecular pathways contributing to sarcomere structure, and muscle function. However, a systematic investigation of the relationship between muscle force and sarcomere organization is lacking. Here, we investigate the contribution of various sarcomere proteins and membrane attachment components to muscle structure and function to introduce C. elegans as a model organism to study the genetic basis of muscle strength. Methods We employ two recently developed assays that involve exertion of muscle forces to investigate the correlation of muscle function to sarcomere organization. We utilized a microfluidic pillar-based platform called NemaFlex that quantifies the maximum exertable force and a burrowing assay that challenges the animals to move in three dimensions under a chemical stimulus. We selected 20 mutants with known defects in various substructures of sarcomeres and compared the physiological function of muscle proteins required for force generation and transmission. We also characterized the degree of sarcomere disorganization using immunostaining approaches. Results We find that mutants with genetic defects in thin filaments, thick filaments, and M-lines are generally weaker, and our assays are successful in detecting the functional changes in response to each sarcomere location tested. We find that the NemaFlex and burrowing assays are functionally distinct informing on different aspects of muscle physiology. Specifically, the burrowing assay has a larger bandwidth in phenotyping muscle mutants, because it could pick ten additional mutants impaired while exerting normal muscle force in NemaFlex. This enabled us to combine their readouts to develop an integrated muscle function score that was found to correlate with the score for muscle structure disorganization. Conclusions Our results highlight the suitability of NemaFlex and burrowing assays for evaluating muscle physiology of C. elegans. Using these approaches, we discuss the importance of the studied sarcomere proteins for muscle function and structure. The scoring methodology we have developed enhances the utility of  C. elegans as a genetic model to study muscle function.

2021 ◽  
Author(s):  
Leila Lesanpezeshki ◽  
Hiroshi Qadota ◽  
Masoud Norouzi Darabad ◽  
Karishma Kashyap ◽  
Carla M. R. Lacerda ◽  
...  

AbstractBackgroundCaenorhabditis elegans has been widely used as a model to study muscle structure and function due to many genes having human homologs. Its body wall muscle is functionally and structurally similar to vertebrate skeletal muscle with conserved molecular pathways contributing to sarcomere structure, and muscle function. However, a systematic investigation of the relationship between muscle force and sarcomere organization is lacking. Here, we investigate the contribution of various sarcomere proteins and membrane attachment components to muscle structure and function to introduce C. elegans as a model organism to study the genetic basis of muscle strength.MethodsWe employ two recently developed assays that involve exertion of muscle forces to investigate the correlation of muscle function to sarcomere organization. We utilized a microfluidic pillar-based platform called NemaFlex that quantifies the maximum exertable force and a burrowing assay that challenges the animals to move in three dimensions under a chemical stimulus. We selected 20 mutants with known defects in various substructures of sarcomeres and compared the physiological function of muscle proteins required for force generation and transmission. We also characterized the degree of sarcomere disorganization using immunostaining approaches.ResultsWe find that mutants with genetic defects in thin filaments, thick filaments and M-lines are generally weaker, and our assays are successful in detecting the functional changes in response to each sarcomere location tested. We find that the NemaFlex and burrowing assays are functionally distinct informing on different aspects of muscle physiology. Specifically, the burrowing assay has a larger bandwidth in phenotyping muscle mutants, because it could pick ten additional mutants impaired while exerting normal muscle force in NemaFlex. This enabled us to combine their readouts to develop an integrated muscle function score that was found to correlate with the score for muscle structure disorganization.ConclusionsOur results highlight the suitability of NemaFlex and burrowing assays for evaluating muscle physiology of C. elegans. Using these approaches, we discuss the importance of the studied sarcomere proteins for muscle function and structure. The scoring methodology we have developed lays the foundation for investigating the contribution of conserved sarcomere proteins and membrane attachment components to human muscle function and strength.


2003 ◽  
Vol 27 (4) ◽  
pp. 171-182
Author(s):  
Susan V. Brooks

Contractions of skeletal muscles provide the stability and power for all body movements. Consequently, any impairment in skeletal muscle function results in some degree of instability or immobility. Factors that influence skeletal muscle structure and function are therefore of great interest both scientifically and clinically. Injury, disease, and old age are among the factors that commonly contribute to impairment in skeletal muscle function. The goal of this article is to update current concepts of skeletal muscle physiology. Particular emphasis is placed on mechanisms of injury, repair, and adaptation in skeletal muscle as well as mechanisms underlying the declining skeletal muscle structure and function associated with aging. For additional materials please refer to the “Skeletal Muscle Physiology” presentation located on the American Physiological Society Archive of Teaching Resources Web site ( https://www.lifescitrc.org ).


2020 ◽  
Vol 118 (3) ◽  
pp. 258a
Author(s):  
Laszlo Csernoch ◽  
Mónika Gönczi ◽  
Zsolt Ráduly ◽  
László Szabó ◽  
Nóra Dobrosi ◽  
...  

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Joshua Mattock ◽  
Julie R. Steele ◽  
Karen J. Mickle

Abstract Background Medial tibial stress syndrome (MTSS) is a common lower leg injury experienced by runners. Although numerous risk factors are reported in the literature, many are non-modifiable and management of the injury remains difficult. Lower leg muscle structure and function are modifiable characteristics that influence tibial loading during foot-ground contact. Therefore, this study aimed to determine whether long-distance runners with MTSS displayed differences in in vivo lower leg muscle structure and function than matched asymptomatic runners. Methods Lower leg structure was assessed using ultrasound and a measure of lower leg circumference to quantify muscle cross-sectional area, thickness and lean lower leg girth. Lower leg function was assessed using a hand-held dynamometer to quantify maximal voluntary isometric contraction strength and a single leg heel raise protocol was used to measure ankle plantar flexor endurance. Outcome variables were compared between the limbs of long-distance runners suffering MTSS (n = 20) and matched asymptomatic controls (n = 20). Means, standard deviations, 95 % confidence intervals, mean differences and Cohen’s d values were calculated for each variable for the MTSS symptomatic and control limbs. Results MTSS symptomatic limbs displayed a significantly smaller flexor hallucis longus cross-sectional area, a smaller soleus thickness but a larger lateral gastrocnemius thickness than the control limbs. However, there was no statistical difference in lean lower leg girth. Compared to the matched control limbs, MTSS symptomatic limbs displayed deficits in maximal voluntary isometric contraction strength of the flexor hallucis longus, soleus, tibialis anterior and peroneal muscles, and reduced ankle plantar flexor endurance capacity. Conclusions Differences in lower leg muscle structure and function likely render MTSS symptomatic individuals less able to withstand the negative tibial bending moment generated during midstance, potentially contributing to the development of MTSS. The clinical implications of these findings suggest that rehabilitation protocols for MTSS symptomatic individuals should aim to improve strength of the flexor hallucis longus, soleus, tibialis anterior and peroneal muscles along with ankle plantar flexor endurance. However, the cross-sectional study design prevents us determining whether between group differences were a cause or effect of MTSS. Therefore, future prospective studies are required to substantiate the study findings.


2021 ◽  
pp. 2100137
Author(s):  
Jeroen L.M. van Doorn ◽  
Francesca Pennati ◽  
Hendrik H.G. Hansen ◽  
Baziel G.M. van Engelen ◽  
Andrea Aliverti ◽  
...  

Respiratory muscle weakness is common in neuromuscular disorders and leads to significant respiratory difficulties. Therefore, reliable and easy assessment of respiratory muscle structure and function in neuromuscular disorders is crucial. In the last decade, ultrasound and MRI emerged as promising imaging techniques to assess respiratory muscle structure and function. Respiratory muscle imaging directly measures the respiratory muscles and, in contrast to pulmonary function testing, is independent of patient effort. This makes respiratory muscle imaging suitable to use as tool in clinical respiratory management and as outcome parameter in upcoming drug trials for neuromuscular disorders, particularly in children. In this narrative review, we discuss the latest studies and technological developments in imaging of the respiratory muscles by US and MR, and its clinical application and limitations. We aim to increase understanding of respiratory muscle imaging and facilitate its use as outcome measure in daily practice and clinical trials.


1991 ◽  
Vol 70 (6) ◽  
pp. 2650-2655 ◽  
Author(s):  
D. C. McKenzie ◽  
L. S. Goodman ◽  
C. Nath ◽  
B. Davidson ◽  
G. O. Matheson ◽  
...  

Six male Quechua Indians (34.0 +/- 1.1 yr, 159.5 +/- 2.1 cm, 60.5 +/- 1.6 kg), life-long residents of La Raya, Peru (4,350-m altitude with an average barometric pressure of 460 Torr), were studied using noninvasive methods to determine the structural and functional changes in the cardiovascular system in response to a 6-wk deacclimation period at sea level. Cardiac output, stroke volume, and left ventricular ejection fractions were determined using radionuclide angiographic techniques at rest and during exercise on a cycle ergometer at 40, 60, and 90% of a previously determined maximal O2 consumption. Subjects at rest were subjected to two-dimensional and M-mode echocardiograms and a standard 12-lead electrocardiogram. Hemoglobin and hematocrit were measured on arrival at sea level by use of a Coulter Stacker S+ analyzer. After a 6-wk deacclimation period, all variables were remeasured using the identical methodology. Hemoglobin values decreased significantly over the deacclimation period (15.7 +/- 1.1 to 13.5 +/- 1.2 g/dl; P less than 0.01). The results indicate that the removal of these high-altitude-adapted natives from 4,300 m to sea level for 6 wk results in only minor changes to the cardiac structure and function as measured by these noninvasive techniques.


2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Viridiana Navarrrete ◽  
Marcos Ayala ◽  
Antonio Rodriguez ◽  
Francisco Villarreal ◽  
Israel Ramirez-Sanchez

1997 ◽  
Vol 82 (5) ◽  
pp. 1397-1405 ◽  
Author(s):  
Yuko Kitagawa ◽  
Stephan F. Van Eeden ◽  
Darlene M. Redenbach ◽  
Maleki Daya ◽  
Blair A. M. Walker ◽  
...  

Kitagawa, Yuko, Stephan F. Van Eeden, Darlene M. Redenbach, Maleki Daya, Blair A. M. Walker, Maria E. Klut, Barry R. Wiggs, and James C. Hogg. Effect of mechanical deformation on structure and function of polymorphonuclear leukocytes. J. Appl. Physiol. 82(5): 1397–1405, 1997.—The present studies were designed to test the hypothesis that mechanical deformation of polymorphonuclear leukocytes (PMN) leads to functional changes that might influence their transit in the pulmonary capillaries. Human leukocytes were passed through 5- or 3-μm-pore polycarbonate filters under controlled conditions. Morphometric analysis showed that the majority of PMN were deformed and that this deformation persisted longer after filtration through 3-μm filters than through 5-μm filters ( P < 0.05) but did not result in the cytoskeletal polarization characteristic of migrating cells. Flow cytometric studies of the filtered PMN showed that there was a transient increase in the cytosolic free Ca2+ concentration after both 3- and 5-μm filtration ( P< 0.01) with an increase in F-actin content after 3-μm filtration ( P < 0.05). AlthoughL-selectin expression on PMN was not changed by either 5- or 3-μm filtration, CD18 and CD11b were increased by 3-μm filtration ( P < 0.05). Priming of the PMN with N-formyl-methionyl-leucyl-phenylalanine (0.5 nM) before filtration resulted in an increase of CD11b by both 5 ( P < 0.05)- and 3-μm ( P < 0.01) filtration. Neither 5- nor 3-μm filtration induced hydrogen peroxide production. We conclude that mechanical deformation of PMN, similar to what occurs in the pulmonary microvessels, induces both structural and functional changes in the cells, which might influence their passage through the pulmonary capillary bed.


Sign in / Sign up

Export Citation Format

Share Document