Cardiac development involves a dynamic interaction of genetic and epigenetic factors. An important epigenetic factor is the biomechanical environment, as defined by the stress and strain fields in the heart. Determining those fields and their influence on morphogenesis requires the interdisciplinary combination of experimental and computational methods. The long-term aim of this research is to determine the link between function and form during cardiovascular morphogenesis. The primary hypothesis is that the biomechanical environment is the fundamental epigenetic factor that modulates growth and morphogenesis during cardiac development. To test his hypothesis, this project develops and experimentally validates a computational modeling system for representing the geometry and biomechanical behavior of the embryonic heart. This computational system, in conjunction with experiments on embryonic chick hearts, determines the biomechanical principles that regulate vermicular growth and morphogenesis during the normal and abnormal cardiac development. the experimental methods include measuring global and local geometry and growth strains under a variety of perturbed conditions, including ventricular pressure alteration, extracellular matrix degradation, and osmotic environment modification.
The specific aims of this project are first to develop geometric modeling and finite element computer codes to conduct a detailed stress analysis of the embryonic heart. These codes will include the effects of complex three dimensional geometry, anisotropy, and muscle activation. Next, algorithms for modeling growth and morphogenesis are developed and incorporated into the system. The algorithms will be validated by modeling various experimental protocols that perturb growth. Finally, the computational system and a series of experiments are used to identify the biomechanical factors responsible for looping of the embryonic heart.
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