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article

Measuring biological materials mechanics with atomic force microscopy ‐ Mechanical unfolding of biopolymers

Juan Carlos Gil‐Redondo, Andreas Weber, José L. Toca‐Herrera

Microscopy Research and Technique > 85 > 8 > 3025 - 3036

Biopolymers, such as polynucleotides, polypeptides and polysaccharides, are macromolecules that direct most of the functions in living beings. Studying the mechanical unfolding of biopolymers provides important information about their molecular elasticity and mechanical stability, as well as their energy landscape, which is especially important in proteins, since their three‐dimensional structure...

article

Nicotinic‐acid derivative BGP‐15 improves diastolic function in a rabbit model of atherosclerotic cardiomyopathy

Daniel Priksz, Nora Lampe, Arpad Kovacs, Melissa Herwig, more

British Journal of Pharmacology > 179 > 10 > 2240 - 2258

Background and Purpose The small molecule BGP‐15 has been reported to alleviate symptoms of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP‐15 in a rabbit model of atherosclerotic cardiomyopathy. Experimental Approach Rabbits were maintained on standard chow (control) or atherogenic diet (hypercholesterolemic) for 16 weeks....

article

Profoundly lower muscle mass and rate of contractile protein synthesis in boys with Duchenne muscular dystrophy

William J. Evans, Mahalakshmi Shankaran, Edward C. Smith, Carl Morris, more

The Journal of Physiology > 599 > 23 > 5215 - 5227

Abstract Boys with Duchenne muscular dystrophy (DMD) experience a progressive loss of functional muscle mass, with fibrosis and lipid accumulation. Accurate evaluation of whole‐body functional muscle mass (MM) in DMD patients has not previously been possible and the rate of synthesis of muscle proteins remains unexplored. We used non‐invasive, stable isotope‐based methods from plasma and urine to...

article

MALDI‐IMS as a Tool to Determine the Myocardial Response to Syndecan‐2‐Selected Mesenchymal Stromal Cell Application in an Experimental Model of Diabetic Cardiomyopathy

Kathleen Pappritz, Oliver Klein, Fengquan Dong, Nazha Hamdani, more

PROTEOMICS – Clinical Applications > 15 > 1 > n/a - n/a

Purpose Mesenchymal stromal cells (MSC) are an attractive tool for treatment of diabetic cardiomyopathy. Syndecan‐2/CD362 has been identified as a functional marker for MSC isolation. Imaging mass spectrometry (IMS) allows for the characterization of therapeutic responses in the left ventricle. This study aims to investigate whether IMS can assess the therapeutic effect of CD362⁺‐selected MSC on...

article

Differences in stability and calcium sensitivity of the Ig domains in titin's N2A region

Colleen M. Kelly, Sophia Manukian, Emily Kim, Matthew J. Gage

Protein Science > 29 > 5 > 1160 - 1171

Titin is a large filamentous protein that spans half a sarcomere, from Z‐disk to M‐line. The N2A region within the titin molecule exists between the proximal immunoglobulin (Ig) region and the PEVK region and protein–protein interactions involving this region are required for normal muscle function. The N2A region consists of four Ig domains (I80–I83) with a 105 amino acid linker region between I80...

article

End‐diastolic force pre‐activates cardiomyocytes and determines contractile force: role of titin and calcium

Aref Najafi, Martijn de Locht, Maike Schuldt, Patrick Schönleitner, more

The Journal of Physiology > 597 > 17 > 4521 - 4531

Abstract Titin functions as a molecular spring, and cardiomyocytes are able, through splicing, to control the length of titin. We hypothesized that together with diastolic [Ca²⁺], titin‐based stretch pre‐activates cardiomyocytes during diastole and is a major determinant of force production in the subsequent contraction. Through this mechanism titin would play an important role in active force development...

article

Relationship of muscle morphology to hip displacement in cerebral palsy: a pilot study investigating changes intrinsic to the sarcomere

Kelly A. Larkin-Kaiser, Jason J. Howard, Timothy Leonard, Venus Joumaa, more

Journal of Orthopaedic Surgery and Research > 2019 > 14 > 1 > 1-9

Background Cerebral palsy (CP) is the most common cause of childhood disability, typified by a static encephalopathy with peripheral musculoskeletal manifestations—most commonly related to spasticity—that are progressive with age. Hip displacement is one of the most common manifestations, observed to lead to painful degenerative arthritis over time. Despite the key role that spasticity-related adductor...

article

The giant titin: how to evaluate its role in cardiomyopathies

Amar Azad, Giulia Poloni, Naeramit Sontayananon, He Jiang, more

Journal of Muscle Research and Cell Motility > 2019 > 40 > 2 > 159-167

Titin, the largest protein known, has attracted a lot of interest in the cardiovascular field in recent years, since the discovery that truncating variants in titin are commonly found in patients with dilated cardiomyopathy. This review will discuss the contribution of variants in titin to inherited cardiac conditions (cardiomyopathies) and how model systems, such as animals and cellular systems,...

article

Differences in Titin and Nebulin Gene Expression in Skeletal Muscles of Rats Chronically Alcoholized by Different Methods

Yu. V. Gritsyna, A. D. Ulanova, N. N. Salmov, A. G. Bobylev, more

Molecular Biology > 2019 > 53 > 1 > 54-63

This work studied the changes in the levels of the main proteins of the calpain system (μ-calpain, Са²⁺-dependent protease, and fragments of its autolysis, inhibitor calpastatin) and μ-calpain substrates (giant proteins of the sarcomere cytoskeleton, titin and nebulin) in skeletal muscle (m. gastrocnemius, m. soleus, m. longissimus dorsi) of rats alcoholized for three months by different methods using...

article

Autoantibodies in acquired myasthenia gravis: Clinical phenotype and immunological correlation

Madhu Nagappa, Anita Mahadevan, Yashwanth Gangadhar, Shripad A. Patil, more

Acta Neurologica Scandinavica > 139 > 5 > 428 - 437

Background Data on antibody profile in myasthenia gravis (MG) from India are limited. Objectives To investigate antibody profile in patients with MG and their clinical correlates. Patients and Methods Patients of MG (n = 85, M:F::1.1:1, mean age: 39.29 ± 17.3 years, mean symptom duration: 72.94 ± 91.8 months) were evaluated for clinical features, MG foundation of America (MGFA) score, response...

article

Titin mutations and muscle disease

Dalma Kellermayer, John E. Smith, Henk Granzier

Pflügers Archiv - European Journal of Physiology > 2019 > 471 > 5 > 673-682

The introduction of next-generation sequencing technology has revealed that mutations in the gene that encodes titin (TTN) are linked to multiple skeletal and cardiac myopathies. The most prominent of these myopathies is dilated cardiomyopathy (DCM). Over 60 genes are linked to the etiology of DCM, but by far, the leading cause of DCM is mutations in TTN with truncating variants in TTN (TTNtvs) associated...

article

A mechanical model of the half-sarcomere which includes the contribution of titin

Irene Pertici, Marco Caremani, Massimo Reconditi

Journal of Muscle Research and Cell Motility > 2019 > 40 > 1 > 29-41

The evidence, in both resting and active muscle, for the presence of an I-band spring element like titin that anchors the Z line to the end of the thick filament did not yet produce a proper theoretical treatment in a complete model of the half-sarcomere. The textbook model developed by A. F. Huxley and his collaborators in 1981, which provides that the half-sarcomere (hs) compliance is due to the...

article

Centronuclear myopathy with cardiomyopathy due to recessive titinopathy

Jennifer M. Martinez‐Thompson, Thomas L. Winder, Teerin Liewluck

Muscle & Nerve > 59 > 4 > E26 - E27

article

Changes in Titin and Collagen Modulate Effects of Aerobic and Resistance Exercise on Diabetic Cardiac Function

Shunchang Li, Min Liang, Derun Gao, Quansheng Su, more

Journal of Cardiovascular Translational Research > 2019 > 12 > 5 > 404-414

Diastolic dysfunction is a common complication that occurs early in diabetes mellitus. Titin and collagen are two important regulators of myocardial passive tension, which contributes to diabetic myocardial diastolic dysfunction. Exercise therapy significantly improves the impaired diabetic cardiac function, but its benefits appear to depend on the type of exercise used. We investigated the effect...

article

Scalable, Non-denaturing Purification of Phosphoproteins Using Ga³⁺-IMAC: N2A and M1M2 Titin Components as Study case

Michael Adams, Jennifer R. Fleming, Eva Riehle, Tiankun Zhou, more

The Protein Journal > 2019 > 38 > 2 > 181-189

The purification of phosphorylated proteins in a folded state and in large enough quantity for biochemical or biophysical analysis remains a challenging task. Here, we develop a new implementation of the method of gallium immobilized metal chromatography (Ga³⁺-IMAC) as to permit the selective enrichment of phosphoproteins in the milligram scale and under native conditions using automated FPLC instrumentation...

article

Expanding the importance of HMERF titinopathy: new mutations and clinical aspects

Johanna Palmio, Sarah Leonard-Louis, Sabrina Sacconi, Marco Savarese, more

Journal of Neurology > 2019 > 266 > 3 > 680-690

Objective Hereditary myopathy with early respiratory failure (HMERF) is caused by titin A-band mutations in exon 344 and considered quite rare. Respiratory insufficiency is an early symptom. A collection of families and patients with muscle disease suggestive of HMERF was clinically and genetically studied. Methods Altogether 12 new families with 19 affected patients and diverse nationalities were...

article

Prediction of folding mechanisms for Ig‐like beta sandwich proteins based on inter‐residue average distance statistics methods

Panyavut Aumpuchin, Takeshi Kikuchi

Proteins: Structure, Function, and Bioinformatics > 87 > 2 > 120 - 135

To understand the folding mechanism of a protein is one of the goals in bioinformatics study. Nowadays, it is enigmatic and difficult to extract folding information from amino acid sequence using standard bioinformatics techniques or even experimental protocols which can be time consuming. To overcome these problems, we aim to extract the initial folding unit for titin protein (Ig and fnIII domains)...

article

Genetics of Dilated Cardiomyopathy

Yiwen Fu, Howard J. Eisen

Current Cardiology Reports > 2018 > 20 > 11 > 1-7

Purpose of Review Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation and systolic function and is the most common among all cardiomyopathies. Familial DCM makes up a significant portion of cases, and approximately 40 genes are identified as involved in the pathogenesis of heart failure, each affecting a specific part of cellular mechanisms. The purpose of this review is to...

article

Changes in degradation and phosphorylation level of titin in three ovine muscles during postmortem

Ying Wang, Xin Li, Zheng Li, Meng Li, more

International Journal of Food Science & Technology > 53 > 4 > 913 - 920

The objective of this study was to investigate the degradation of titin and its phosphorylation level in three muscles from sheep. The MFI and pH from the longissimus lumborum (LL), semimembranosus (SM) and psoas major (PM) muscles were measured at 30 min, 1, 2, 7, 14, 21 and 28 days postmortem. Myofibrillar proteins were extracted, separated by SDS‐PAGE and quantified by phosphor‐specific staining...

article

The multiple roles of titin in muscle contraction and force production

Walter Herzog

Biophysical Reviews > 2018 > 10 > 4 > 1187-1199

Titin is a filamentous protein spanning the half-sarcomere, with spring-like properties in the I-band region. Various structural, signaling, and mechanical functions have been associated with titin, but not all of these are fully elucidated and accepted in the scientific community. Here, I discuss the primary mechanical functions of titin, including its accepted role in passive force production, stabilization...

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Search results

Measuring biological materials mechanics with atomic force microscopy ‐ Mechanical unfolding of biopolymers

Nicotinic‐acid derivative BGP‐15 improves diastolic function in a rabbit model of atherosclerotic cardiomyopathy

Profoundly lower muscle mass and rate of contractile protein synthesis in boys with Duchenne muscular dystrophy

MALDI‐IMS as a Tool to Determine the Myocardial Response to Syndecan‐2‐Selected Mesenchymal Stromal Cell Application in an Experimental Model of Diabetic Cardiomyopathy

Differences in stability and calcium sensitivity of the Ig domains in titin's N2A region

End‐diastolic force pre‐activates cardiomyocytes and determines contractile force: role of titin and calcium

Relationship of muscle morphology to hip displacement in cerebral palsy: a pilot study investigating changes intrinsic to the sarcomere

The giant titin: how to evaluate its role in cardiomyopathies

Differences in Titin and Nebulin Gene Expression in Skeletal Muscles of Rats Chronically Alcoholized by Different Methods

Autoantibodies in acquired myasthenia gravis: Clinical phenotype and immunological correlation

Titin mutations and muscle disease

A mechanical model of the half-sarcomere which includes the contribution of titin

Centronuclear myopathy with cardiomyopathy due to recessive titinopathy

Changes in Titin and Collagen Modulate Effects of Aerobic and Resistance Exercise on Diabetic Cardiac Function

Scalable, Non-denaturing Purification of Phosphoproteins Using Ga³⁺-IMAC: N2A and M1M2 Titin Components as Study case

Expanding the importance of HMERF titinopathy: new mutations and clinical aspects

Prediction of folding mechanisms for Ig‐like beta sandwich proteins based on inter‐residue average distance statistics methods

Genetics of Dilated Cardiomyopathy

Changes in degradation and phosphorylation level of titin in three ovine muscles during postmortem

The multiple roles of titin in muscle contraction and force production

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