scholarly journals Computational modelling of muscle fibre operating ranges in the hindlimb of a small ground bird (Eudromia elegans), with implications for modelling locomotion in extinct species

2021 ◽  
Vol 17 (4) ◽  
pp. e1008843
Author(s):  
Peter J. Bishop ◽  
Krijn B. Michel ◽  
Antoine Falisse ◽  
Andrew R. Cuff ◽  
Vivian R. Allen ◽  
...  
Keyword(s):  
Muscle Function ◽  
Computational Models ◽  
Fibre Length ◽  
Computational Modelling ◽  
Length Change ◽  
Muscle Fibres ◽  
Extinct Species ◽  
Length Changes ◽  
Experimental Findings

The arrangement and physiology of muscle fibres can strongly influence musculoskeletal function and whole-organismal performance. However, experimental investigation of muscle function during in vivo activity is typically limited to relatively few muscles in a given system. Computational models and simulations of the musculoskeletal system can partly overcome these limitations, by exploring the dynamics of muscles, tendons and other tissues in a robust and quantitative fashion. Here, a high-fidelity, 26-degree-of-freedom musculoskeletal model was developed of the hindlimb of a small ground bird, the elegant-crested tinamou (Eudromia elegans, ~550 g), including all the major muscles of the limb (36 actuators per leg). The model was integrated with biplanar fluoroscopy (XROMM) and forceplate data for walking and running, where dynamic optimization was used to estimate muscle excitations and fibre length changes throughout both gaits. Following this, a series of static simulations over the total range of physiological limb postures were performed, to circumscribe the bounds of possible variation in fibre length. During gait, fibre lengths for all muscles remained between 0.5 to 1.21 times optimal fibre length, but operated mostly on the ascending limb and plateau of the active force-length curve, a result that parallels previous experimental findings for birds, humans and other species. However, the ranges of fibre length varied considerably among individual muscles, especially when considered across the total possible range of joint excursion. Net length change of muscle–tendon units was mostly less than optimal fibre length, sometimes markedly so, suggesting that approaches that use muscle–tendon length change to estimate optimal fibre length in extinct species are likely underestimating this important parameter for many muscles. The results of this study clarify and broaden understanding of muscle function in extant animals, and can help refine approaches used to study extinct species.

scholarly journals The Digital Mouse: why computational modelling of mouse models of disease can improve translation

2020 ◽  
Author(s):  
Natal van Riel ◽  
Ralph Müller ◽  
Enrico Dall’Ara
Keyword(s):  
Animal Models ◽  
Chronic Diseases ◽  
In Silico ◽  
Computational Models ◽  
Frailty Index ◽  
Computational Modelling ◽  
List Type ◽  
Age Related ◽  
Experimental Findings

AbstractComputational models can be used to study the mechanistic phenomena of disease. Current mechanistic computer simulation models mainly focus on (patho)physiology in humans. However, often data and experimental findings from preclinical studies are used as input to develop such models. Biological processes underlying age-related chronic diseases are studied in animal models. The translation of these observations to clinical applications is not trivial. As part of a group of international scientists working in the COST Action network MouseAGE, we argue that in order to boost the translation of pre-clinical research we need to develop accurate in silico counterparts of the in vivo animal models. The Digital Mouse is proposed as framework to support the development of evidence-based medicine, for example to develop geroprotectors, which are drugs that target fundamental mechanisms of ageing.HighlightsComputational modelling of human (patho)physiology is advancing rapidly, often using and extrapolating experimental findings from preclinical disease models.The lack of in silico models to support in vivo modelling in mice is a missing link in current approaches to study complex, chronic diseases.The development of mechanistic computational models to simulate disease in mice can boost the discovery of novel therapeutic interventions.The ‘Digital Mouse’ is proposed as a framework to implement this ambition. The development of a Digital Mouse Frailty Index (DM:FI) to study aging and age-related diseases is provided as an example.

Muscle function during jumping in frogs. I. Sarcomere length change, EMG pattern, and jumping performance

1996 ◽  
Vol 271 (2) ◽  
pp. C563-C570 ◽  
Author(s):  
G. J. Lutz ◽  
L. C. Rome
Keyword(s):  
Mechanical Properties ◽  
Muscle Function ◽  
Length Change ◽  
Operating Conditions ◽  
Mechanical Power ◽  
Shortening Velocity ◽  
Jumping Performance ◽  
Angular Velocities ◽  
High Level

We determined the influence of temperature on muscle function during jumping to better understand how the frog muscular system is designed to generate a high level of mechanical power. Maximal jumping performance and the in vivo operating conditions of the semimembranosus muscle (SM), a hip extensor, were measured and related to the mechanical properties of the isolated SM in the accompanying paper [Muscle function during jumping in frogs. II. Mechanical properties of muscle: implication for system design. Am. J. Physiol. 271 (Cell Physiol. 40): C571-C578, 1996]. Reducing temperature from 25 to 15 degrees C caused a 1.75-fold decline in peak mechanical power generation and a proportional decline in aerial jump distance. The hip and knee joint excursions were nearly the same at both temperatures. Accordingly, sarcomeres shortened over the same range (2.4 to 1.9 microns) at both temperatures, corresponding to myofilament overlap at least 90% of maximal. At the low temperature, however, movements were made more slowly. Angular velocities were 1.2- to 1.4-fold lower, and ground contact time was increased by 1.33-fold at 15 degrees C. Average shortening velocity of the SM was only 1.2-fold lower at 15 degrees C than at 25 degrees C. The low Q10 of velocity is in agreement with that predicted for muscles shortening against an inertial load.

The Medial Patellofemoral Ligament Is a Dynamic and Anisometric Structure: An In Vivo Study on Length Changes and Isometry

2019 ◽  
Vol 47 (7) ◽  
pp. 1645-1653 ◽  
Author(s):  
Willem A. Kernkamp ◽  
Cong Wang ◽  
Changzou Li ◽  
Hai Hu ◽  
Ewoud R.A. van Arkel ◽  
...  
Keyword(s):  
Knee Flexion ◽  
Medial Patellofemoral Ligament ◽  
Length Change ◽  
High Rate ◽  
Mpfl Reconstruction ◽  
Full Extension ◽  
3 Dimensional ◽  
Technical Errors ◽  
Length Changes

Background: Medial patellofemoral ligament (MPFL) reconstruction is associated with a high rate of complications, including recurrent instability and persistent knee pain. Technical errors are among the primary causes of these complications. Understanding the effect of adjusting patellofemoral attachments on length change patterns may help surgeons to optimize graft placement during MPFL reconstruction and to reduce graft failure rates. Purpose: To determine the in vivo length changes of the MPFL during dynamic, weightbearing motion and to map the isometry of the 3-dimensional wrapping paths from various attachments on the medial femoral epicondyle to the patella. Study Design: Descriptive laboratory study. Methods: Fifteen healthy participants were studied with a combined computed tomography and biplane fluoroscopic imaging technique during a lunge motion (full extension to ~110° of flexion). On the medial femoral epicondyle, 185 attachments were projected, including the anatomic MPFL footprint, which was divided into 5 attachments (central, proximal, distal, posterior, and anterior). The patellar MPFL area was divided into 3 possible attachments (proximal, central, and distal). The length changes of the shortest 3-dimensional wrapping paths of the various patellofemoral combinations were subsequently measured and mapped. Results: For the 3 patellar attachments, the most isometric attachment, with an approximate 4% length change, was located posterior and proximal to the anatomic femoral MPFL attachment, close to the adductor tubercle. Attachments proximal and anterior to the isometric area resulted in increasing lengths with increasing knee flexion, whereas distal and posterior attachments caused decreasing lengths with increasing knee flexion. The anatomic MPFL was tightest in extension, decreased in length until approximately 30° of flexion, and then stayed near isometric for the remainder of the motion. Changing both the femoral and patellar attachments significantly affected the length changes of the anatomic MPFL ( P < .001 for both). Conclusion: The most isometric location for MPFL reconstruction was posterior and proximal to the anatomic femoral MPFL attachment. The anatomic MPFL is a dynamic, anisometric structure that was tight in extension and early flexion and near isometric beyond 30° of flexion. Clinical Relevance: Proximal and anterior MPFL tunnel positioning should be avoided, and the importance of anatomic MPFL reconstruction is underscored with the results found in this study.

scholarly journals The anatomical arrangement of muscle and tendon enhances limb versatility and locomotor performance

2011 ◽  
Vol 366 (1570) ◽  
pp. 1540-1553 ◽  
Author(s):  
Alan Wilson ◽  
Glen Lichtwark
Keyword(s):  
Muscle Contraction ◽  
Relative Length ◽  
Length Change ◽  
Measurement Methods ◽  
Muscle Fibres ◽  
Locomotor Performance ◽  
Trade Offs ◽  
Anatomical Arrangement ◽  
Relative Length Change

The arrangement of muscles and tendons has been studied in detail by anatomists, surgeons and biomechanists for over a century, and the energetics and mechanics of muscle contraction for almost as long. Investigation of how muscles function during locomotion and the relative length change in muscle fibres and the associated elastic tendon has, however, been more challenging. In recent years, novel in vivo measurement methods such as ultrasound and sonomicrometry have contributed to our understanding of the dynamics of the muscle tendon unit during locomotion. Here, we examine both published and new data to explore how muscles are arranged to deliver the wide repertoire of locomotor function and the trade-offs between performance and economy that result.

IN VIVO MUSCLE LENGTH CHANGES IN BUMBLEBEES AND THE IN VITRO EFFECTS ON WORK AND POWER

1993 ◽  
Vol 183 (1) ◽  
pp. 101-113 ◽  
Author(s):  
K. M. Gilmour ◽  
C. P. Ellington
Keyword(s):  
High Speed ◽  
Time Course ◽  
Second Harmonic ◽  
Muscle Length ◽  
Muscle Fibres ◽  
Bombus Lucorum ◽  
Length Changes ◽  
In Vitro Effects

The amplitude and time course of muscle length changes were examined in vivo in tethered, flying bumblebees Bombus lucorum. A ‘window’ was cut in the dorsal cuticle and aluminium particles were placed on the exposed dorsal longitudinal muscle fibres. Muscle oscillations were recorded using high-speed video and a high-magnification lens. The amplitude of muscle length changes was 1.9 % (s.d.=0.5 %, N=7), corresponding to the commonly quoted strain of 1–3 % for asynchronous muscle. Higher harmonics, particularly the second, were found in the muscle oscillations and in the wing movements. The second harmonic for wing movements was damped in comparison to that for muscle length changes, probably as a result of compliance in the thoracic linkage. Inclusion of the second harmonic in the driving signal for in vitro experiments on glycerinated fibres generally resulted in a decrease in the work and power, but a substantial increase was found for some fibres.

MYOTOMAL MUSCLE FUNCTION AT DIFFERENT LOCATIONS IN THE BODY OF A SWIMMING FISH

1993 ◽  
Vol 182 (1) ◽  
pp. 191-206 ◽  
Author(s):  
J. D. Altringham ◽  
C. S. Wardle ◽  
C. I. Smith
Keyword(s):  
Power Output ◽  
Muscle Function ◽  
Muscle Activation ◽  
Muscle Power ◽  
Travelling Waves ◽  
The Body ◽  
Muscle Fibres ◽  
Cycle Frequency ◽  
Lateral Muscle

We describe experiments on isolated, live muscle fibres which simulate their in vivo activity in a swimming saithe (Pollachius virens). Superficial fast muscle fibres isolated from points 0.35, 0.5 and 0.65 body lengths (BL) from the anterior tip had different contractile properties. Twitch contraction time increased from rostral to caudal myotomes and power output (measured by the work loop technique) decreased. Power versus cycle frequency curves of rostral fibres were shifted to higher frequencies relative to those of caudal fibres. In the fish, phase differences between caudally travelling waves of muscle activation and fish bending suggest a change in muscle function along the body. In vitro experiments indicate that in vivo superficial fast fibres of rostral myotomes are operating under conditions that yield maximum power output. Caudal myotomes are active as they are lengthened in vivo and initially operate under conditions which maximise their stiffness, before entering a positive power-generating phase. A description is presented for the generation of thrust at the tail blade by the superficial, fast, lateral muscle. Power generated rostrally is transmitted to the tail by stiffened muscle placed more caudally. A transition zone between power generation and stiffening travels caudally, and all but the most caudal myotomes generate power at some phase of the tailbeat. Rostral power output, caudal force, bending moment and force at the tail blade are all maximal at essentially the same moment in the tailbeat cycle, as the tail blade crosses the swimming track.

scholarly journals Scaling Effects on Muscle Function: Power Output of Isolated Fish Muscle Fibres Performing Oscillatory Work

1990 ◽  
Vol 151 (1) ◽  
pp. 453-467 ◽  
Author(s):  
JOHN D. ALTRINGHAM ◽  
IAN A. JOHNSTON
Keyword(s):  
Power Output ◽  
Fibre Length ◽  
Fish Muscle ◽  
Maximum Power ◽  
Muscle Fibres ◽  
Scaling Effects ◽  
Cycle Frequency ◽  
Maximum Power Output ◽  
Wide Range ◽  
Length Changes

Bundles of 3–10 live fast fibres were isolated from the abdominal myotomes of cod (Gadus morhua L.) 13–67 cm in length. The preparations performed work under conditions simulating their activity during swimming: sinusoidal length changes were imposed about in situ fibre length, and the fibres were stimulated at a selected phase in each cycle. Strain amplitude, and the number and timing of stimuli were chosen to give maximum power output over a wide range of cycle/tailbeat frequencies. For each preparation power output was maximal at a particular frequency, although the peaks were rather broad. As the size of the fish increased the cycle frequency for maximum power output (fopt) decreased, from 12.5 Hz (13 cm fish) to 5 Hz (67 cm fish) (fopt= 1.67 L−0.52, where L is body length).

scholarly journals Evaluation of a modified Cheatham-Platinum stent for the treatment of aortic coarctation by finite element modelling

2018 ◽  
Vol 7 ◽  
pp. 204800401877395 ◽  
Author(s):  
Barbara EU Burkhardt ◽  
Nicholas Byrne ◽  
Marí Nieves Velasco Forte ◽  
Francesco Iannaccone ◽  
Matthieu De Beule ◽  
...  
Keyword(s):  
Finite Element ◽  
Aortic Coarctation ◽  
Computational Models ◽  
Three Dimensional ◽  
Computational Modelling ◽  
Patient Specific ◽  
Stent Design ◽  
Initial Length ◽  
Element Analysis

Objectives Stent implantation for the treatment of aortic coarctation has become a standard approach for the management of older children and adults. Criteria for optimal stent design and construction remain undefined. This study used computational modelling to compare the performance of two generations of the Cheatham-Platinum stent (NuMED, Hopkinton, NY, USA) deployed in aortic coarctation using finite element analysis. Design Three-dimensional models of both stents, reverse engineered from microCT scans, were implanted in the aortic model of one representative patient. They were virtually expanded in the vessel with a 16 mm balloon and a pressure of 2 atm. Results The conventional stent foreshortened to 96.5% of its initial length, whereas the new stent to 99.2% of its initial length. Diameters in 15 slices across the conventional stent were 11.6–15 mm (median 14.2 mm) and slightly higher across the new stent: 10.7–15.3 mm (median 14.5 mm) (p= 0.021). Apposition to the vessel wall was similar: conventional stent 31.1% and new stent 28.6% of total stent area. Conclusions The new design Cheatham-Platinum stent showed similar deployment results compared to the conventional design. The new stent design showed slightly higher expansion, using the same delivery balloon. Patient-specific computational models can be used for virtual implantation of new aortic stents and promise to inform subsequent in vivo trials.

scholarly journals ST6GAL1-mediated heterogeneity in sialic acid levels potentiates invasion of breast cancer epithelia

2020 ◽  
Author(s):  
Dharma Pally ◽  
Durjay Pramanik ◽  
Shahid Hussain ◽  
Shreya Verma ◽  
Anagha Srinivas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sialic Acid ◽  
Cell Surface ◽  
Single Cells ◽  
Computational Modelling ◽  
Cancer Cell Line ◽  
Sialic Acids ◽  
Cellular Potts Model ◽  
Experimental Findings

AbstractHeterogeneity in phenotypes of malignantly transformed cells and aberrant glycan expression on their surface are two prominent hallmarks of cancers that have hitherto not been linked to each other. In this paper, we identify heterogeneity in a specific glycan linkage: α2,6-linked sialic acids within breast cancer cells in vivo and in culture. Upon sorting out two populations with moderate and relatively higher cell surface α2,6-linked sialic acid levels from the triple negative breast cancer cell line MDA-MB-231, both populations (denoted as medium and high-2,6-Sial cells respectively) stably retained their levels in early passages. Upon continuous culturing, medium 2,6-Sial cells recapitulated the heterogeneity of the unsorted line whereas high 2,6-Sial cells showed no such tendency. Compared with the high 2,6-Sial, the medium 2,6-Sial cells showed greater adhesion to reconstituted extracellular matrices (ECM) as well as invaded faster as single cells. The level of α2,6-linked sialic acids in the two sublines was found to be consistent with the expression of a specific glycosyl transferase, ST6GAL1. Stably knocking down ST6GAL1 in the high 2,6-Sial cells, enhanced their invasiveness. When cultured together, medium 2,6-Sial cells differentially migrated to the edge of growing tumoroid-like cultures, whereas high 2,6-Sial cells formed the central bulk. Simulations in a Cellular Potts model-based computational environment that is calibrated to our experimental findings suggest that the heterogeneity of cell-ECM adhesion, likely regulated by α2,6-linked sialic acids facilitates niches of highly invasive cells to efficiently migrate centrifugally as the invasive front of a malignant tumor.Significance StatementCell-surface sugars are aberrantly expressed in cancer but their contributions to tumor heterogeneity are not known. In this study, we uncover and separate breast cancer populations with distinct α2,6-linked sialic acid levels. The moderately expressing population shows stronger adhesion to extracellular matrix than the high expressing population. It also invades faster through the matrix as single cells. Combining experiments with computational modelling, we show that the heterogeneity in matrix adhesion is vital to accentuating cell invasion. In some conditions, invasion of heterogeneous populations may compare with, or exceed that of, homogeneous moderately expressing populations. Our findings are vital to furthering our understanding of how cancers spread and potentially qualify efforts to manage the disease through glycan-editing or immunotherapeutic approaches.

Energetics and power output of isolated fish fast muscle fibres performing oscillatory work

1991 ◽  
Vol 158 (1) ◽  
pp. 261-273 ◽  
Author(s):  
T. W. Moon ◽  
J. D. Altringham ◽  
I. A. Johnston
Keyword(s):  
High Performance ◽  
Energy Charge ◽  
Fibre Length ◽  
Creatine Phosphate ◽  
High Energy ◽  
Rapid Decline ◽  
Muscle Fibres ◽  
Tight Coupling ◽  
Work Cycle

Fast myotomal muscle fibres were isolated from the cod (Gadus morhua L.) and the energy cost of contraction was measured under conditions simulating swimming. Fibre bundles were subjected to sinusoidal cycles of shortening and lengthening about their in situ fibre length, and stimulated at selected phases in each cycle. The preparations were poisoned with iodoacetic acid and bubbled with nitrogen to block the synthesis of ATP. After an initial rapid decline over the first 10 cycles, force and net work remained steady in some cases for up to 64 oscillatory length cycles, but more commonly declined slowly after about 30 cycles. The total mechanical work performed increased largely in proportion to the number of work cycles. At the end of each experiment fibres were frozen in isopentane cooled in liquid nitrogen and metabolite concentrations determined by high performance liquid chromatography (HPLC) and enzymatic analysis. Concentrations of adenylates did not differ significantly from control values, although a significant increase in IMP concentrations at 64 cycles accounted for the maintenance of relatively high energy charge values. Creatine (C) concentrations increased and creatine phosphate (CP) concentrations decreased, implying a tight coupling of the ATP/ADP reaction to the CP/C reaction. Muscle economy was calculated as the positive work performed during a work cycle divided by the total chemical energy expended. These values (approx. 7 mJ mumol-1) were found to be independent of the number of work cycles performed, although a trend to increase was observed. Muscle efficiency values, calculated assuming a Gibb's force free energy change for CP splitting in vivo of 55 kJ mol-1, were in the range 12–23%.

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