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.

Public Health Relevance

The human swallow is an instinctive and precisely orchestrated act whose goal is to transport ingested food from the mouth to the esophagus. Central to this process is the stereotypical deformation of the tongue, a versatile and structurally complex muscular organ. While numerous studies have addressed the physiological motions of the tongue during the swallow, the study of intramural structure and function has long been impeded by the complexity of the tongue's myoarchitecture and associated mechanics. Our approach considers lingual mechanics as the multi-scale behavior of the tissue, and is intended to define the mechanism by which the tongue's complex array of components contribute to the force generation necessary for coordinated and well controlled performance 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. We postulate that the human tongue creates forceful hydrostatic deformations that may be modeled as the activation of meso-scale myofiber tracts derived from MRI. The material and activation properties constituting these myofiber tracts may in turn be derived from the structural, biochemical, and mechanical attributes of the constituting myofilaments and their regulation in the skeletal myocyte. Our research will focus on the generation of a multi-scale model of lingual mechanical function, substantiated by evolving knowledge of its underlying biophysical and biomechanical attributes. Based on this approach, it should be feasible to re- define lingual disease in terms of quantitative measures of myoarchitecture and mechanical function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC011528-06
Application #
8661745
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Shekim, Lana O
Project Start
2011-03-10
Project End
2016-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
6
Fiscal Year
2014
Total Cost
$528,406
Indirect Cost
$188,595
Name
Northeastern University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001423631
City
Boston
State
MA
Country
United States
Zip Code
02115