Multiscale mechanisms of lingual mechanical function

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): The tongue is an intricately configured muscular organ that plays a vital role during swallowing, first to configure and then to propel the ingested bolus from the oral cavity to the pharynx. Disorders of lingual mechanical function are exceedingly common in the elderly and patients with neurological diseases, and may be responsible for malnutrition and increased risk of aspiration pneumonia in these patients. Notwithstanding, there is little understanding of the way in which the lingual musculature contributes to the tissue's physiological function. Determining how the tongue functions during swallowing requires an understanding of the organ's movements in relation to extrinsic structures as well as fundamental relationships involving intramural structure and function. These relationships epitomize the more general physiological tenet that articulated tongue motion results from the intricate balance of internal (contractile) and external (adhesion, mechanical tethering) forces acting on and generated by myocytes. Our approach considers lingual mechanics and motion in terms of its multiscale attributes, and is intended to define the mechanism by which the tongue's exquisitely complex array of components contribute to coordinated and well controlled force generation during swallowing. To address this goal, our laboratory has developed new technologies, including high resolution MRI, methods to assay and represent myofilament and cell mechanics, and a computational framework capable of quantifying mechanical performance across spatial scales. MRI defines complex tissue myoarchitecture and mechanics in terms of intermediate-scale, i.e. meso-scale, anatomical structures (myofiber tracts) and provides anatomical and biomechanical input into FE multiscale analysis of tongue function. We postulate that mesoscale myofiber tract arrays defined by diffusion weighted MRI dictate patterns of coordinated force generation and deformation during swallowing. The material and activation properties constituting these myofiber tracts are in turn derived principally from myofilament biology and relationships associated with the underlying skeletal myocytes. Our research will focus on the generation of a finite element model of lingual function, substantiated by evolving knowledge of its underlying biophysical, mechanical, and physiological attributes. To address this goal, we propose the following Specific Aims: Aim 1: To formulate a biophysical model of lingual skeletal muscle contractility combining cell geometry, cytoskeletal structures and myofilament interactions. Aim 2: To derive 3D relationships between the contractility of aligned myocytes and tissue deformation via the mechanics of multi-cellular myofiber tracts during human swallowing. Aim 3: To develop a finite element model (FEM) of lingual deformation during swallowing based on biophysical principles of skeletal muscle function and the mechanics of myofiber tracts derived by MRI. Based on the concepts proposed here, it should be feasible to consider lingual mechanics during swallowing in terms of quantitative measures of myoarchitecture and mechanics. Knowledge of the underlying mechanical mechanisms associated with lingual force production should allow the design of more specific therapies to address oral and pharyngeal dysphagia.