Computational Model for Early Cardiac Looping

2006

Developmental Dynamics

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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.

“…1, 2A). All of these constraints apply mechanical loads that likely influence looping morphology (Manasek, 1983;Voronov and Taber, 2002;Voronov et al, 2004;Ramasubramanian et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

Morphogenetic adaptation of the looping embryonic heart to altered mechanical loads

Nerurkar

Ramasubramanian

2006

Developmental Dynamics

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“…These include the models for invagination of Davidson et al (1995) and Munoz et al (2007), as well as the finite element model for cardiac looping of Ramasubramanian et al (2006). In addition, Hardin and Cheng (1986) used a model to study secondary invagination during gastrulation in the sea urchin.…”

Section: Previous Models For Epithelial Morphogenesismentioning

confidence: 99%

Theoretical study of Beloussov’s hyper-restoration hypothesis for mechanical regulation of morphogenesis

Biomech Model Mechanobiol

2007

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Computational models were used to explore the idea that morphogenesis is regulated, in part, by feedback from mechanical stress according to Beloussov's Hyper-restoration (HR) Hypothesis. According to this hypothesis, active tissue responses to stress perturbations restore, but overshoot, the original (target) stress. To capture this behavior, the rate of growth or contraction is assumed to depend on the difference between the current and target stresses. Stress overshoot is obtained by letting the target stress change at a rate proportional to the same stress difference. The feasibility of the HR Hypothesis is illustrated by models for stretching of epithelia, cylindrical bending of plates, invagination of cylindrical and spherical shells, and early amphibian development. In each case, an initial perturbation leads to an active mechanical response that changes the form of the tissue. The results show that some morphogenetic processes can be entirely self-driven by HR responses once they are initiated (possibly by genetic activity). Other processes, however, may require secondary mechanisms or perturbations to proceed to completion.

“…Finally, Ramasubramanian et al (2006) have presented a three-dimensional FE model for early heart development (looping) that was developed in ABAQUS using the techniques introduced here. This model includes simultaneous application of various morphogenetic processes such as growth, cytoskeletal contraction, and active cell-shape changes.…”

Section: Relation To Previous Models For Morphogenesismentioning

confidence: 99%

Computational modeling of morphogenesis regulated by mechanical feedback

Ramasubramanian

Biomech Model Mechanobiol

2007

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Mechanical forces cause changes in form during embryogenesis and likely play a role in regulating these changes. This paper explores the idea that changes in homeostatic tissue stress (target stress), possibly modulated by genes, drive some morphogenetic processes. Computational models are presented to illustrate how regional variations in target stress can cause a range of complex behaviors involving the bending of epithelia. These models include growth and cytoskeletal contraction regulated by stress-based mechanical feedback. All simulations were carried out using the commercial finite element code ABAQUS, with growth and contraction included by modifying the zero-stress state in the material constitutive relations. Results presented for bending of bilayered beams and invagination of cylindrical and spherical shells provide insight into some of the mechanical aspects that must be considered in studying morphogenetic mechanisms.