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PubMed2000

Relationship between arterial elasticity indices and carotid artery intima-media thickness.

Functional and structural changes of the arterial wall appear to serve as early hallmarks of the hypertensive disease process. Structural vascular changes can be studied by the determination of the intima-media wall thickness (IMT) at the carotid artery. The elastic behavior of the proximal and distal parts of the arterial tree can be assessed from noninvasively recorded radial artery waveforms. The aim of the study was to compare large (proximal, C1) and small (distal, C2) artery elasticity indices in two age-matched study groups with high- and low-normal blood pressure (BP) and to assess the relation between elasticity indices and IMT. A total number of 22 subjects with high-normal BP (40 +/- 2 years; BP, 147 +/- 2.5/84 +/- 1.5 mm Hg) and 22 matched controls with low-normal BP (40 +/- 2 years; BP, 123 +/- 1.9/69 +/- 1.5 mm Hg) were enrolled. The IMT was echographically determined at the common carotid artery by the leading-edge technique. Large artery (C1) and small artery (C2) elasticity indices were calculated from a third-order, four-element model of the arterial circulation. In the group with high-normal BP large and small artery elasticity indices were significantly decreased versus controls with low-normal BP (C1: 1.63 +/- 0.08 v 1.99 +/- 0.09 mL/mm Hg, P < .01; C2: 0.059 +/- 0.005 v 0.076 +/- 0.007 mL/ mm Hg, P < .05) and IMT increased significantly (0.607 +/- 0.039 v 0.516 +/- 0.027 mm, P < .05). Moreover, there was an inverse relationship between IMT and small artery elasticity index (r = -0.60, P = .004). In subjects with a high-normal BP there is already a change in the IMT of the carotid artery versus normotension. The IMT is related to the small artery elasticity index (C2).

Adult↗
PubMed1997

Organization of collagen and elastic fibers studied in stretch preparations of whole mounts of human visceral pleura.

Fibers of the collagenous and elastic systems are most relevant in the double mechanical action of visceral pleura (VP), i.e. volume limitation and the generation of elastic recoil pressure. In this work we studied the organization of these fibrous components of VP in two situations: normal lungs and bullous disease. We employed histochemical methods on conventional histological slides and on thin spreads of whole mounts of visceral pleura. In addition, the scanning electron microscope was also used. According to our results, pleural function is made possible by the combination of both the elastic and collagenous fiber systems, each one having as intrinsic organizational pattern. Marked alterations of pleural bullous structure are observed with changes in lung volume. Fibers of the elastic and collagenous systems are clearly interdependent elements. Collagenous fibers are interwoven in a plaited structure that closely resembles the osiers of a wicker basket, indicating that collagen fibers allow for lung volume increase up to a point of maximal stretching of the system. The pleural contribution to lung elastic recoil pressure originates from the elastic network which turns back to its resting position when inspiratory pressures are negligible. The pleural immobility in bullous disease is associated with an almost complete absence of elastic fibers and the presence of very thick collagen fibers, suggestive of a cicatricial process, devoid of any characteristic pattern of distribution.

Collagen↗
PubMed2003

Elastic fiber production in cardiovascular tissue-equivalents.

Elastic fiber incorporation is critical to the success of tissue-engineered arteries and heart valves. Elastic fibers have not yet been observed in tissue-engineered replacements fabricated in vitro with smooth muscle cells. Here, rat smooth muscle cells (SMC) or human dermal fibroblasts (HDF) remodeled collagen or fibrin gels for 4 weeks as the basis for a completely biological cardiovascular tissue replacement. Immunolabeling, alkaline extraction and amino acid analysis identified and quantified elastin. Organized elastic fibers formed when neonatal SMC were cultured in fibrin gel. Fibrillin-1 deposition occurred but elastin was detected in regions without fibrillin-1, indicating that a microfibril template is not required for elastic fiber formation within fibrin. Collagen did not support substantial elastogenesis by SMC. The quantity of crosslinked elastic fibers was enhanced by treatment with TGF-beta1 and insulin, concomitant with increased collagen production. These additives overcame ascorbate's inhibition of elastogenesis in fibrin. The elastic fibers that formed in fibrin treated with TGF-beta1 and insulin contained crosslinks, as evidenced by the presence of desmosine and an altered elastin labeling pattern when beta-aminopropionitrile (BAPN) was added. These findings indicate that in vitro elastogenesis can be achieved in tissue engineering applications, and they suggest a physiologically relevant model system for the study of three-dimensional elastic structures.

Amino Acids↗
PubMed1995

Osteopontin is a constitutive component of normal elastic fibers in human skin and aorta.

Osteopontin is an acidic matrix protein, mainly expressed in mineralized tissues, kidney and atherosclerotic vessels; its biological role is still largely undefined. In the present study, immunocytochemical approaches showed that osteopontin is localized within normal elastic fibers of human skin and aorta. Antibodies raised against human bone osteopontin (LF7) or against human osteopontin synthetic peptide (amino acids 1-10, LF19) recognized epitopes associated with the amorphous material within the elastic fibers. Elastic fiber-associated microfibrils were always negative. The positivity for osteopontin of the elastic fibers was independent of age and could be observed in fetal skin and aorta as well as in the same of children, young adults and old subjects. The altered elastic fibers in the skin of old individuals were only fairly positive for osteopontin. The presence of osteopontin within the elastic fibers suggests that it may play a role against the observed tendency of elastic fibers to favor mineral precipitation. A role of osteopontin in modulating crystal nucleation and growth in mineralizing tissues and, more generally, in conditions in which mineral precipitation should be controlled is also possible.

Adolescent↗
PubMed1997

Medial elastic structure alterations in atherosclerotic arteries in minipigs: plaque proximity and arterial site specificity.

Using a model of atherosclerosis in minipigs, we analyzed changes in elastic structure within the medial sections of the abdominal aorta and left interventricular coronary artery both in the vicinity of and distal to atheromatous plaques. Twenty-four animals, divided into three groups, were fed either a control diet or a hypercholesterolemic and hyperhomocysteinic atherogenic diet, alone or in association with an antihypertensor, namely isosorbide dinitrate (Risordan). The atherogenic diet, administered for a period of four months, induced in the minipig advanced noncalcified atherosclerotic lesions that were histologically similar to those found in humans. A morphodensitometric analysis of the medial elastic structures was carried out on images obtained from specifically stained transverse arterial sections examined under a light microscope. The volume density of the elastic structures was diminished in the arterial media of the atherosclerotic animals due to opening and widening of the fenestrae in the elastic laminate and increased communication between the interlamellar spaces. Whereas this elastolytic process was uniform and independent of the proximity of atheromatous plaques in the left interventricular coronary artery, it was intensified in the vicinity of the plaques in the abdominal aorta. Overall elastolytic activity was increased in the walls of atheromatous artery in both arterial sites, and metalloproteinases were implied in this increase of activity. We previously reported that treatment with isosorbide dinitrate significantly reduced the moderate systolic hypertension and the increase in transparietal stress observed in the abdominal aorta of atheromatous animals. We report here that isosorbide dinitrate prevented the atherogenic-diet-induced deterioration of the elastic structure in these arteries; complete inhibition of changes to the elastic laminae was evident in areas remote from plaque formation, but only partial inhibition in the vicinity of such plaques. It did not, however, prevent structural damage in the left interventricular coronary artery or modify the increase in parietal elastolytic activity in either of the two arteries. This suggests that damage to the elastic structure in atheromatous arteries is dependent not only on overall elastolytic activity but also on localized factors, possibly related to parietal stresses, affected by the presence of atheromatous plaques.

Amino Acids↗
PubMed2006

Elastic fibres in health and disease.

Elastic fibres are a major class of extracellular matrix fibres that are abundant in dynamic connective tissues such as arteries, lungs, skin and ligaments. Their structural role is to endow tissues with elastic recoil and resilience. They also act as an important adhesion template for cells, and they regulate growth factor availability. Mutations in major structural components of elastic fibres, especially elastin, fibrillins and fibulin-5, cause severe, often life-threatening, heritable connective tissue diseases such as Marfan syndrome, supravalvular aortic stenosis and cutis laxa. Elastic-fibre function is also frequently compromised in damaged or aged elastic tissues. The ability to regenerate or engineer elastic fibres and tissues remains a significant challenge, requiring improved understanding of the molecular and cellular basis of elastic-fibre biology and pathology, and ability to regulate the spatiotemporal expression and assembly of its molecular components.

Animals↗
PubMed2001

Cholesterol decreases the interfacial elasticity and detergent solubility of sphingomyelins.

The interfacial interactions of cholesterol with sphingomyelins (SMs) containing various homogeneous acyl chains have been investigated by Langmuir film balance approaches. Low in-plane elasticity among the packed lipids was identified as an important physical feature of the cholesterol-sphingomyelin liquid-ordered phase that correlates with detergent resistance, a characteristic property of sphingolipid-sterol rafts. Changes in the in-plane elastic packing, produced by cholesterol, were quantitatively assessed by the surface compressional moduli (C(s)(-1)) of the monolayer isotherms. Of special interest were C(s)(-1) values determined at high surface pressures (>30 mN/m) that mimic the biomembrane situation. To identify structural features that uniquely affect the in-plane elasticity of the sphingomyelin-cholesterol lateral interaction, comparisons were made with phosphatidylcholine (PC)-cholesterol mixtures. Cholesterol markedly decreased the in-plane elasticity of either SM or PC regardless of whether they were fluid or gel phase without cholesterol. The magnitude of the reduction in in-plane elasticity induced by cholesterol was strongly influenced by acyl chain structure and by interfacial functional groups. Liquid-ordered phase formed at lower cholesterol mole fractions when SM's acyl chain was saturated rather than monounsaturated. At similar high cholesterol mole fractions, the in-plane elasticity within SM-cholesterol liquid-ordered phase was significantly lower than that of PC-cholesterol liquid-ordered phase, even when PCs were chain-matched to the SMs. Sphingoid-base functional groups (e.g., amide linkages), which facilitate or strengthen intermolecular hydrogen bonds, appear to be important for forming sphingomyelin-cholesterol, liquid-ordered phases with especially low in-plane elasticity. The combination of structural features that predominates in naturally occurring SMs permits very effective resistance to solubilization by Triton X-100.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1986

Elasticity of synthetic phospholipid vesicles and submitochondrial particles during osmotic swelling.

A rapid and accurate method has been developed for measuring the elastic response of vesicle bilayer membranes to an applied osmotic pressure. The technique of dynamic light scattering is used to measure both the elastic constant and the elastic limit of dioleoylphosphatidic acid (DOPA) and DOPA-cholesterol vesicles and of submitochondrial particles derived from the inner membrane of bovine heart mitochondria. The vesicles prepared by the pH-adjustment method are unilamellar and of uniform size between 240 and 460 nm in diameter. The vesicles swell uniformly upon dilution. The observed change in size is not due to any change in the shape of the vesicles. The data also indicate that the vesicles are spherical and not flaccid. The total vesicle swelling in these studies resulted in a 3-4% increase in surface area for vesicles swollen in 0.15 M KCl and a 5-10% increase in surface area for vesicles swollen in 0.25 M sucrose. This maximum represents the elastic limit of the vesicles. Evidence is presented to show that the vesicles release contents after swelling to this maximum, reseal immediately, and reswell according to the osmotic pressure. For DOPA vesicles in a 0.15 M KCl-tris(hydroxymethyl)aminomethane hydrochloride (Tris-HCl) buffer (pH 7.55), the observed membrane modulus is found to be in the range of 10(8) dyn/cm2. The modulus was found to be in the order of 10(7) dyn/cm2 for DOPA vesicles in a 0.25 M sucrose-Tris-HCl buffer (pH 7.55). This is comparable to that of submitochondrial particles in the same sucrose-Tris-HCl buffer. The observed membrane modulus also decreases with vesicle size. Its magnitude and its variation with ionic strength indicate that the major component of bilayer elasticity is neither the inherent elasticity of the bilayer nor the bending modulus. The variation of the membrane modulus with respect to curvature suggests that its principal component may be related to surface tension effects including the negative charges on the vesicle surface. There is considerable variation between vesicles swollen in sucrose and those swollen in KCl in the membrane modulus, in the elastic limit at which the vesicles burst, and in the transbilayer pressure difference at bursting. The latter was found to be 4-6 mosM (10(5) dyn/cm2) in sucrose solution and 20-4 mosM (10(6) dyn/cm2) in KCl solution.

Animals↗
PubMed2001

Sarcomeric visco-elasticity of chemically skinned skeletal muscle fibres of the rabbit at rest.

The giant muscle protein titin (connectin), contained in the gap filament that connect a thick filament to the Z-line in a sarcomere, is generally considered to be responsible for the passive force (tension) and visco-elasticity in resting striated muscle. However, whether it can account for all the features of the resting tension response remains unclear. In this paper, we examine the basic features of the 'sarcomeric visco-elasticity' in a single resting mammalian muscle fibre and attempt to account for various tension components on the basis of known structural features of a sarcomere. At sarcomere length of approximately 2.6 microm, the force response to a ramp stretch of 2-5% is complex but can be resolved into four functionally different components. The behaviour displayed by the components ranges from pure viscous type (directly proportional to stretch velocity, ranging from 0.1 to 30 lengths s(-1)) to predominantly elastic type (insensitive to stretch velocity at 1-2 s time scale); simulations show two components of visco-elasticity with characteristically different relaxation times. The velocity-sensitive components (only) are enhanced by filament lattice compression (dextran - 500 kD) and by increased medium viscosity (dextran - 12 kD); also, the relaxation time of visco-elasticity is longer with increased medium viscosity. Amplitude of all the components and the relaxation time of visco-elasticity are increased at longer sarcomere length (range approximately 2.5 - 3.0 microm). The study, and quantitative analyses, extend our previous work on intact muscle fibres and suggest that the velocity-sensitive tension components in intact sarcomere arise from interactions between sarcomeric filaments, filament segments and inter-filamentary medium; the two components of visco-elasticity arise from distinct regions of titin (connectin) molecules.

Animals↗
PubMed2004

Differential distribution of elastic tissue in human natural skin and tissue-engineered skin.

Tissue-engineered skins (TES), manufactured by epidermal and dermal equivalents, are now being used in biological, pharmacotoxicological and clinical applications. It is thus interesting to know to what extent artificial organs are similar to natural counterparts. Elastic fibres are important constituents of the extracellular matrix of natural skin (NS). The aim of our study was to investigate the possible occurrence and distribution of elastic tissue in a model of human TES using different histochemical techniques, including classical Orcein and Fuchsin-Resorcin methods and immunohistochemistry, at both light and electron microscopical levels. Immunoperoxidase and high resolution immunogold methods were used. In NS, classical staining techniques and elastin-immunohistochemistry revealed a well-organized network of elastic fibres. High resolution immunocytochemistry revealed an intense labelling in the amorphous component of elastic fibres. Fibres of different diameters were immunostained. In TES, no stained elastic fibres were observed using classical staining techniques, and the interpretation of immunoperoxidase observations was not clear-cut. In contrast, immunogold staining at the electron microscopical level provided specific labelling of elastin-like immunoreactive material in the dermal equivalent. However, ultrastructural immunocytochemistry revealed that elastic tissue organization in TES was poor compared to that in NS. This study demonstrates that elastic fibres are a component of the extracellular matrix in this model of TES and suggests that fibroblasts of the dermal equivalent are engaged in matrix secretion. Nevertheless, the level of extracellular matrix organization in TES is low compared to NS. Moreover, this study also suggests that different models of bilayered TES may differ with respect to extracellular matrix organization. These aspects should be considered when TES is used in biological and pharmacotoxicological studies. A better understanding of the factors influencing extracellular matrix formation in TES is necessary to achieve further development of skin generation in vitro.

Cells, Cultured↗
PubMed2000

Elastic tissue in scars and alopecia.

A recent report suggests that elastic fibers appear in scars in a time-dependent fashion. This observation prompted our investigation, because we have found elastic tissue stains helpful in determining the pattern of scarring in cases of permanent alopecia. We carried out this investigation to determine if the Verhoeff-Van Gieson (VVG) elastic stain can reliably differentiate scarred from non-scarred dermis and to test our hypothesis that elastic stained sections are helpful in distinguishing lichen planopilaris (LPP) from lupus erythematosus (LE), central progressive alopecia in black females ("follicular degeneration syndrome" and "hot comb alopecia" are other terms used to describe this condition) and classic ivory white idiopathic pseudopelade. We studied histological sections from surgical scars of known duration, stained with the VVG elastic stain and VVG-stained sections of scalp biopsies from patients with established lesions of permanent alopecia. In most cases, both vertical and transverse sections were examined. In every case, the VVG stain clearly differentiated scar from the normal surrounding dermis. Distinct patterns of elastic tissue allowed for correct classification in most of the well-established cases of permanent alopecia studied. We determined that the Verhoeff-Van Gieson stain is an excellent stain to evaluate the pattern of scarring in cases of permanent alopecia and elastic tissue stains may be helpful in the histological evaluation of alopecia.

Alopecia↗
PubMed2002

Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo.

Extracellular elastic fibres provide mechanical elasticity to tissues and contribute towards the processes of organ remodelling by affecting cell-cell signalling. The formation of elastic fibres requires the assembly and crosslinking of tropoelastin monomers, and organization of the resulting insoluble elastin matrix into functional fibres. The molecules and mechanisms involved in this process are unknown. Fibulin-5 (also known as EVEC/DANCE) is an extracellular matrix protein abundantly expressed in great vessels and cardiac valves during embryogenesis, and in many adult tissues including the aorta, lung, uterus and skin, all of which contain abundant elastic fibres. Here we show that fibulin-5 is a calcium-dependent, elastin-binding protein that localizes to the surface of elastic fibres in vivo. fibulin-5-/- mice develop marked elastinopathy owing to the disorganization of elastic fibres, with resulting loose skin, vascular abnormalities and emphysematous lung. This phenotype, which resembles the cutis laxa syndrome in humans, reveals a critical function for fibulin-5 as a scaffold protein that organizes and links elastic fibres to cells. This function may be mediated by the RGD motif in fibulin-5, which binds to cell surface integrins, and the Ca2+-binding epidermal growth factor (EGF) repeats, which bind elastin.

Amino Acid Sequence↗
PubMed1991

Extent of pulmonary emphysema in man and its relation to the loss of elastic recoil.

1. We assessed lung density, determined by computerized tomography, as a measure of emphysema and related this to lung function and measurement of the elastic recoil of the lung in normal subjects and patients with chronic obstructive lung disease. 2. We found a significant correlation between measurements of elastic recoil pressure at 90% of total lung capacity and both the forced expiratory volume in 1 s (r = 0.80, P less than 0.001) and the transfer factor for carbon monoxide (r = 0.70, P less than 0.001). Measurements of elastic recoil of the lung also correlated with lung density as measured by computerized tomography scanning (P less than 0.001). 3. Multiple regression analysis demonstrated a correlation between the density of the lowest fifth percentile of the computerized tomography lung-density histogram, and both the natural logarithm of the shape parameter of the pressure-volume curve (P less than 0.01), and the transfer factor for carbon monoxide (P less than 0.01). However, the mean computerized tomography lung density correlated, in addition, with the elastic recoil pressure of the lungs at 90% of total lung capacity (P less than 0.001). 4. Since the elastic recoil pressure correlates with computerized tomography lung density, and hence with emphysema, and since elastic recoil pressure also correlates with the forced expiratory volume in 1 s, these results suggest that loss of elastic recoil is one determinant of airflow limitation in patients with chronic obstructive lung disease.

Adult↗
PubMed2006

Orthodontic latex elastics: a force relaxation study.

The objectives of this study were to assess the force relaxation of latex elastics occurring within 24 hours of extension and to estimate the extension required to reach the reported force. Five specimens of various manufacturers' latex elastics size and force levels were mounted on a custom-made setup capable of monitoring force levels in real time with a continuous mode and without operator intervention. The percentage of force relaxation was estimated from the initial and 24-hour levels, and the results were analyzed with one-way analysis of variance and the Tukey test at alpha = 0.05 level of significance. The elastics showed force relaxation in the order of 25%, which consisted of an initial high slope component and a latent part of decreased rate. Most relaxation occurred within the first 3-5 hours after extension, regardless of size, manufacturer, or force level of the elastic. The overall as well as the initial relaxation curves were fitted to equations, which described the variation of force with time. Elastic extension to achieve the reported force was found to range between 2.7 and five times the original length. Latex elastics show force relaxation in the order of 25%, which consists of an initial high slope component and a latent part of decreased rate. Most relaxation occurs within the first 3-5 hours after extension, regardless of size, manufacturer, or force level of the elastic. The empirical rule of "3" shows remarkable variation, ranging from 2.7 to five.

Elasticity↗
PubMed2001

Effect of exposing dentine to sodium hypochlorite and calcium hydroxide on its flexural strength and elastic modulus.

AIM: The aim of this study was to evaluate the effect of sodium hypochlorite (NaOCl) solutions (3%, 5%) and saturated calcium hydroxide (Ca(OH)2) solution, individually and consecutively, on the flexural strength and modulus of elasticity of standardized dentine bars. METHODOLOGY: Standardized plano-parallel dentine bars (n = 121) were divided into five test groups and one control group. The control group 1 consisted of dentine bars, stored in normal saline until testing. The dentine bars in the five test groups were treated by exposure to the following solutions; group 2--3% NaOCl, 2 h; group 3--5% NaOCl, 2 h; group 4--saturated Ca(OH)2 solution, 1 week; group 5--3% NaOCl, 2 h and then saturated Ca(OH)2 solution 1 week; group 6--5% NaOCl, 2 h and then saturated Ca(OH)2 solution 1 week. The dentine bars were then loaded to failure in a three-point bend test. RESULTS: The data revealed a significant (P < 0.001) decrease in the modulus of elasticity and flexural strength of the dentine bars treated with 3% and 5% NaOCl. There was no significant difference in the flexural strength and the modulus of elasticity between the 3% and 5% NaOCl groups. Exposure to Ca(OH)2 significantly (P < 0.001) reduced the flexural strength but had no significant effect on the modulus of elasticity. The groups treated with sodium hypochlorite followed by calcium hydroxide did not have moduli of elasticity and flexural strengths that were significantly different from those treated only with sodium hypochlorite. CONCLUSIONS: NaOCl (3 & 5%) reduced the modulus of elasticity and flexural strength of dentine. Saturated Ca(OH)2 reduced the flexural strength of dentine but not the modulus of elasticity. Sequential use of NaOCl and Ca(OH)2 has no additional weakening effect.

Calcium Hydroxide↗
PubMed2002

Female gender increases stiffness of elastic but not of muscular arteries in type I diabetic patients.

The reason for the particularly increased risk for cardiovascular complications in diabetic women is still unclear. We have previously found decreased distensibility of elastic arteries in type I diabetic women, indicating increased cardiac load, not seen in type I diabetic men, which might be one contributing factor. Whether the effect of gender is different in muscular arteries in type I diabetic patients has not been assessed. As estimates of arterial distensibility we measured stiffness (beta) and pressure strain elastic modulus (Ep) in the muscular common femoral artery using echo-tracking sonography in 30 women (mean age 34 years, range 20-61) and 26 men (mean age 38 years, range 22-56) with type I diabetes. The results were compared with those of 89 healthy individuals of corresponding age and gender and with previously published results from elastic arteries in these patients obtained at the same occasion. The internal common femoral diameter was significantly decreased in both diabetic men and women. In sharp contrast to the highly significant decreased distensibility of the elastic abdominal aorta and common carotid artery in the type I diabetic women, the distensibility of the common femoral artery did not clearly differ between patients and controls, neither for women nor for men. Thus, the gender difference in changes of arterial distensibility found in elastic arteries was absent or far less obvious in the femoral artery. In conclusion, female gender seems to affect the mechanical properties of elastic, but not of large muscular arteries in type I diabetic patients. Thus, putative gender differences in arterial changes in type I diabetes are to be sought in elastic rather than muscular arteries.

Adult↗
PubMed2000

Calibration of force extension and force degradation characteristics of orthodontic latex elastics.

The force-extension characteristics of orthodontic elastics made of natural rubber latex by 4 manufacturers were subjected to static testing under dry and wet conditions. The elastics consisted of 3 sizes: 3/16, 1/4, and 5/16 inch lumen sizes, each with forces specified according to the standard extension index of three times the lumen diameter. Most of the elastics did not match the specified index using the dry tests, but this should not be a serious clinical concern as all elastics showed acceptable regularity of force-extension characteristics. There was notable force degradation of all elastics when subject to water immersion, approximating 30% during the hour, but with an average less than 7% further loss up to 3 days. There were significant differences in force extension and force degradation characteristics between different extensions and force magnitudes for the elastics of the different manufacturers. It is suggested that the clinician could use the table of force degradation values for different extensions to select an appropriate elastic.

Calibration↗
PubMed2002

Mutation of the myosin converter domain alters cross-bridge elasticity.

Elastic distortion of a structural element of the actomyosin complex is fundamental to the ability of myosin to generate motile forces. An elastic element allows strain to develop within the actomyosin complex (cross-bridge) before movement. Relief of this strain then drives filament sliding, or more generally, movement of a cargo. Even with the known crystal structure of the myosin head, however, the structural element of the actomyosin complex in which elastic distortion occurs remained unclear. To assign functional relevance to various structural elements of the myosin head, e.g., to identify the elastic element within the cross-bridge, we studied mechanical properties of muscle fibers from patients with familial hypertrophic cardiomyopathy with point mutations in the head domain of the beta-myosin heavy chain. We found that the Arg-719 --> Trp (Arg719Trp) mutation, which is located in the converter domain of the myosin head fragment, causes an increase in force generation and fiber stiffness under isometric conditions by 48-59%. Under rigor and relaxing conditions, fiber stiffness was 45-47% higher than in control fibers. Yet, kinetics of active cross-bridge cycling were unchanged. These findings, especially the increase in fiber stiffness under rigor conditions, indicate that cross-bridges with the Arg719Trp mutation are more resistant to elastic distortion. The data presented here strongly suggest that the converter domain that forms the junction between the catalytic and the light-chain-binding domain of the myosin head is not only essential for elastic distortion of the cross-bridge, but that the main elastic distortion may even occur within the converter domain itself.

Cardiomyopathy, Hypertrophic, Familial↗