Multiscale mechanisms of lingual mechanical function

舌机械功能的多尺度机制

• 批准号: 8277622
• 负责人: Richard J Gilbert
• 金额: $ 58.16万
• 依托单位: GENESYS RESEARCH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-10 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277622
• 关键词: Address; Adhesions; Aspiration Pneumonia; Behavior; Biochemical; Biochemical Process; Biological Assay; Biology; Biomechanics; Bolus Infusion; Calcium; Cells; Cellular Structures; Complex; Contracts; Data; Deglutition; Deglutition Disorders; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Elements; Equilibrium; Esophagus; Fiber; Filament; Food; Generations; Goals; Health; Human; Image; Isometric Exercise; Kinetics; Knowledge; Laboratories; Link; Magnetic Resonance Imaging; Malnutrition; Measures; Mechanics; Methodology; Methods; Microfilaments; Modeling; Molecular; Molecular Models; Motion; Movement; Mus; Muscle; Muscle Cells; Muscle Fibers; Muscle function; Muscle relaxation phase; Oral cavity; Organ; Oropharyngeal; Patients; Pattern; Performance; Pharyngeal structure; Physiological; Play; Process; Production; Property; Regulation; Research; Resolution; Risk; Role; Series; Simulate; Skeletal Muscle; Slide; Stress; Structure; Testing; Time; Tissues; Tongue; Work; base; computer framework; design; molecular modeling; multi-scale modeling; nervous system disorder; neuromuscular; new technology; older patient; research study; vector

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.

描述（由申请人提供）：舌头是一个复杂构造的肌肉器官，在吞咽过程中起着至关重要的作用，首先构造，然后将摄入的食团从口腔推进到咽部。舌机械功能障碍在老年人和神经系统疾病患者中非常常见，可能是这些患者营养不良和吸入性肺炎风险增加的原因。尽管如此，有很少的了解，舌肌组织有助于组织的生理功能。确定舌头在吞咽过程中的功能需要了解器官与外部结构的运动以及涉及壁内结构和功能的基本关系。这些关系概括了更普遍的生理学原理，即舌运动是由内部（收缩）和外部（粘附、机械束缚）力作用于肌细胞并由肌细胞产生的复杂平衡引起的。我们的方法认为，舌力学和运动的多尺度属性，并打算定义的机制，舌头的精致复杂的组件阵列有助于协调和良好控制的吞咽过程中产生的力量。为了实现这一目标，我们的实验室开发了新技术，包括高分辨率MRI、分析和表示肌丝和细胞力学的方法，以及能够量化跨空间尺度机械性能的计算框架。MRI定义了复杂的组织肌结构和力学的中等规模，即中尺度，解剖结构（肌纤维束），并提供解剖和生物力学输入到FE多尺度分析的舌功能。 我们假设，中尺度肌纤维束阵列定义的弥散加权MRI支配模式协调的力量产生和变形吞咽。构成这些肌纤维束的材料和活化特性又主要来源于肌丝生物学和与潜在骨骼肌细胞相关的关系。我们的研究将集中在生成一个有限元模型的语言功能，证实了不断发展的知识，其基本的生物物理，机械和生理属性。为了实现这一目标，我们提出了以下具体目标：目标1：制定一个生物物理模型的舌骨骼肌收缩结合细胞几何形状，细胞骨架结构和肌丝相互作用。目标二：通过人类吞咽过程中多细胞肌纤维束的力学推导出对齐的肌细胞收缩性和组织变形之间的3D关系。目标三：根据骨骼肌功能的生物物理学原理和MRI导出的肌纤维束力学，建立吞咽过程中舌变形的有限元模型。基于这里提出的概念，它应该是可行的，以考虑在吞咽过程中的肌结构和力学的定量测量舌力学。与舌力产生相关的潜在机械机制的知识应该允许设计更具体的治疗方法来解决口腔和咽部吞咽困难。