Biomedical subjects

Larry A Taber

Publications and source records attributed to Larry A Taber.

12 recordsLinked to original sources

PubMed2006

Myosin-based contraction is not necessary for cardiac c-looping in the chick embryo.

During the initial phase of cardiac looping, known as c-looping, the heart bends and twists into a c-shaped tube with the convex outer curvature normally directed toward the right side of the embryo. Despite intensive study for more than 80 years, the biophysical mechanisms that drive and regulate looping remain poorly understood, although some investigators have speculated that differential cytoskeletal contraction supplies the driving force for c-looping. The purpose of this investigation was to test this hypothesis. To inhibit contraction, embryonic chick hearts at stages 10-12 (10-16 somites, 33-48 h) were exposed to the myosin inhibitors 2,3-butanedione monoxime (BDM), ML-7, Y-27632, and blebbistatin. Experiments were conducted in both whole embryo culture and, to focus on bending alone, isolated heart culture. Measurements of heart stiffness and phosphorylation of the myosin regulatory light chains showed that BDM, Y-27632, and blebbistatin significantly reduced myocardial contractility, while ML-7 had a lesser effect. None of these drugs significantly affected looping during the studied stages. These results suggest that active contraction is not required for normal c-looping of the embryonic chick heart between stages 10 and 12.

Amides↗

PubMed2006

Morphogenetic adaptation of the looping embryonic heart to altered mechanical loads.

The biophysical mechanisms that drive and regulate cardiac looping are not well understood, but mechanical forces likely play a central role. Previous studies have shown that cardiac torsion, which defines left-right directionality, is caused largely by forces exerted on the heart tube by a membrane called the splanchnopleure (SPL). Here we show that, when the SPL is removed from the embryonic chick heart, torsion is initially suppressed. Several hours later, however, normal torsion is restored. This delayed torsion coincides with increased myocardial stiffness, especially on the right side of the heart. Exposure to the myosin inhibitor Y-27632 suppressed both responses, suggesting that the delayed torsion is caused by an abnormal cytoskeletal contraction. This hypothesis is supported further by computational modeling. These results suggest that the looping embryonic heart has the ability to adapt to changes in the mechanical environment, which may play a regulatory role during morphogenesis.

Amides↗

PubMed2006

Computational model for early cardiac looping.

Looping is a vital event during early cardiac morphogenesis, as the initially straight heart tube bends and twists into a curved tube, laying out the basic pattern of the future four-chambered heart. Despite intensive study for almost a century, the biophysical mechanisms that drive this process are not well understood. To explore a recently proposed hypothesis for looping, we constructed a finite element model for the embryonic chick heart during the first phase of looping, called c-looping. The model includes the main structures of the early heart (heart tube, omphalomesenteric veins, and dorsal mesocardium), and the analysis features realistic three-dimensional geometry, nonlinear passive and active material properties, and anisotropic growth. As per our earlier hypothesis for c-looping, actin-based morpho-genetic processes (active cell shape change, cytoskeletal contraction, and cell migration) are simulated in specific regions of the model. The model correctly predicts the initial gross morphological shape changes of the heart, as well as distributions of morphogenetic stresses and strains measured in embryonic chick hearts. The model was tested further in studies that perturbed normal cardiac morphogenesis. The model, taken together with the new experimental data, supports our hypothesis for the mechanisms that drive early looping.

Animals↗

PubMed2006

Biophysical mechanisms of cardiac looping.

During early embryogenesis, the heart is a single, relatively straight tube which bends and twists (loops) rightward to create the basic plan of the mature heart. Despite intensive study for many decades, the biophysical mechanisms which drive and regulate cardiac looping have remained poorly understood. This review discusses, from a historical perspective, studies of looping mechanics and various theories which have been proposed for this complex process. Then, based on recently acquired data, a new biomechanical hypothesis is proposed for the rst phase of looping (c-looping). Understanding morphogenetic mechanisms would facilitate research devoted to preventing and treating congenital heart malformations caused by looping abnormalities.

Animals↗

PubMed2005

Role of actin polymerization in bending of the early heart tube.

During cardiac c-looping, the heart transforms from a straight tube into a c-shaped tube, presenting the first evidence of left-right asymmetry in the embryo. C-looping consists of two primary deformation components: ventral bending and dextral rotation. This study examines the role of actin polymerization in bending of the heart tube. Exposure of stage 9-11 chick embryos to low concentrations of the actin polymerization inhibitors cytochalasin D (5 nM-2.0 microM) and latrunculin A (LA; 25 nM-2.0 microM) suppressed looping in a stage- and concentration-dependent manner in both whole embryos and isolated hearts. Local exposure of either the dorsal or ventral sides of isolated hearts to LA also inhibited looping, but less than global exposure, indicating that both sides contribute to the bending mechanism. Taken together, these data suggest that ongoing actin polymerization is required for the bending component of cardiac c-looping, and we speculate that polymerization-driven myocardial cell shape changes cause this deformation.

Abnormalities, Drug-Induced↗

PubMed2004

The role of mechanical forces in dextral rotation during cardiac looping in the chick embryo.

Cardiac looping is a vital morphogenetic process that transforms the initially straight heart tube into a curved tube normally directed toward the right side of the embryo. While recent work has brought major advances in our understanding of the genetic and molecular pathways involved in looping, the biophysical mechanisms that drive this process have remained poorly understood. This paper examines the role of biomechanical forces in cardiac rotation during the initial stages of looping, when the heart bends and rotates into a c-shaped tube (c-looping). Embryonic chick hearts were subjected to mechanical and chemical perturbations, and tissue stress and strain were studied using dissection and fluorescent labeling, respectively. The results suggest that (1) the heart contains little or no intrinsic ability to rotate, as external forces exerted by the splanchnopleure (SPL) and the omphalomesenteric veins (OVs) drive rotation; (2) unbalanced forces in the omphalomesenteric veins play a role in left-right looping directionality; and (3) in addition to ventral bending and rightward rotation, the heart tube also bends slightly toward the right. The results of this study may help investigators searching for the link between gene expression and the mechanical processes that drive looping.

Actins↗

PubMed2004

On the effects of residual stress in microindentation tests of soft tissue structures.

Microindentation methods are commonly used to determine material properties of soft tissues at the cell or even sub-cellular level. In determining properties from force-displacement (FD) data, it is often assumed that the tissue is initially a stress-free, homogeneous, linear elastic half-space. Residual stress, however, can strongly influence such results. In this paper, we present a new microindentation method for determining both elastic properties and residual stress in soft tissues that, to a first approximation, can be regarded as a pre-stressed layer embedded in or adhered to an underlying relatively soft, elastic foundation. The effects of residual stress are shown using two linear elastic models that approximate specific biological structures. The first model is an axially loaded beam on a relatively soft, elastic foundation (i.e., stress-fiber embedded in cytoplasm), while the second is a radially loaded plate on a foundation (e.g., cell membrane or epithelium). To illustrate our method, we use a nonlinear finite element (FE) model and experimental FD and surface contour data to find elastic properties and residual stress in the early embryonic chick heart, which, in the region near the indenter tip, is approximated as an isotropic circular plate under tension on a foundation. It is shown that the deformation of the surface in a microindentation test can be used along with FD data to estimate material properties, as well as residual stress, in soft tissue structures that can be regarded as a plate under tension on an elastic foundation. This method may not be as useful, however, for structures that behave as a beam on a foundation.

Animals↗

PubMed2004

Material properties and residual stress in the stage 12 chick heart during cardiac looping.

During the morphogenetic process of cardiac looping, the initially straight cardiac tube bends and twists into a curved tube. The biophysical mechanisms that drive looping remain unknown, but the process clearly involves mechanical forces. Hence, it is important to determine mechanical properties of the early heart, which is a muscle-wrapped tube consisting primarily of a thin outer layer of myocardium surrounding a thick extracellular matrix compartment known as cardiac jelly. In this work, we used microindentation experiments and finite element modeling, combined with an inverse computational method, to determine constitutive relations for the myocardium and cardiac jelly at the outer curvature of stage 12 chick hearts. Material coefficients for exponential strain-energy density functions were found by fitting force-displacement and surface displacement data near the indenter Residual stress in the myocardium also was estimated. These results should be useful for computational models of the looping heart.

Animals↗

PubMed2003

Regional epicardial strain in the embryonic chick heart during the early looping stages.

Epicardial strains were measured in Hamburger-Hamilton stage 11 and 12 embryonic chick hearts (1.6-2.0 days of incubation). These stages include part of the early phase of cardiac looping, as the initially straight heart tube bends and twists to form a curved c-shaped tube. By analyzing the motion of microbeads placed on the myocardial surface, we measured strains near the outer curvature, in the central region, and near the inner curvature of the primitive ventricle. No significant differences in strain were found between stages. Relative to end diastole, all three regions shortened by about 10% during systole in the circumferential direction, and the outer curvature shortened longitudinally by about 5%. In contrast, and unlike strains in older hearts, the inner curvature and central regions elongated by approximately 5-10% in the longitudinal direction during systole. These results are consistent with microstructural data and suggest that the material properties of the outer curvature are relatively isotropic, whereas the properties of the central and inner curvature regions are orthotropic, with contractile stress exerted primarily in the circumferential direction.

Aging↗

PubMed2003

Mechanical asymmetry in the embryonic chick heart during looping.

Cardiac looping, which begins with ventral bending and rightward rotation of the primitive heart tube, is an essential morphogenetic event that occurs early in vertebrate development. The biophysical mechanism that drives this process is unknown. It has been speculated that increased stiffness along the dorsal side of the ventricle combined with an intrinsic cardiac force causes the heart to bend. There is no experimental support for this hypothesis, however, since little is known about regional mechanical properties of the heart during looping. We directly measured diastolic stiffness of the inner curvature (IC), outer curvature (OC), and dorsal-ventral sides of the stage 12 chick heart by microindentation. The IC of intact hearts was found to be significantly stiffer than either the OC or the sides. which were of similar stiffness. Isolated cardiac jelly, which is a thick, extracellular matrix compartment underlying the myocardium, was approximately an order of magnitude softer than intact hearts. The results of a computational model simulating the indentation experiments, combined with the stiffness measurements, suggests the regional variation in stiffness is due to the material properties of the myocardium. A second model shows that a relatively stiff IC may facilitate bending of the heart tube during looping.

Animals↗

PubMed2002

Cardiac looping in experimental conditions: effects of extraembryonic forces.

The chick embryo is a popular experimental model used to study the mechanisms of cardiac looping. To facilitate oxygen transport, researchers typically culture the embryo on the surface of the medium. Such preparations, however, expose the embryo and the heart to surface tension that is not present in ovo. This study investigates the influence that surface and extraembryonic membrane tensions have on looping morphology. To eliminate surface tension, we developed a technique in which the embryo is cultured under a thin layer of fluid. To eliminate membrane tension, the membrane was removed. Our results show that both tensions can affect looping, with surface tension potentially having a much greater effect. Moreover, we show that surface tension can alter results in one classic looping experiment.

Animals↗

PubMed2002

Intramyocardial pressure measurements in the stage 18 embryonic chick heart.

Intramyocardial pressure (IMP) and ventricular pressure (VP) were measured in the trabeculating heart of the stage 18 chick embryo (3 days of incubation). Pressure was measured at several locations across the ventricle using a fluid-filled servo-null system. Maximum systolic and minimum diastolic IMP tended to be greater in the dorsal wall than in the ventral wall, but transmural distributions of peak active (maximum minus minimum) IMP were similar in both walls. Peak active IMP near midwall was similar to peak active VP, but peak active IMP in the subepicardial and subendocardial layers was four to five times larger. These results suggest that the passive stiffness of the dorsal wall is greater than that of the ventral wall and that during contraction the inner and outer layers of both walls generate more contractile force and/or become less permeable to flow than the middle part of the wall. Measured pressures likely correspond to regional variations in wall stress that may influence morphogenesis and function in the embryonic heart.

Animals↗