Multiscale mechanisms of lingual mechanical function

描述(申请人提供)：舌头是一个复杂的肌肉器官，在吞咽过程中起着至关重要的作用，首先是形成吞咽，然后推动吞咽的推进剂从口腔到咽部。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，人们对舌肌如何对组织的生理功能做出贡献却知之甚少。确定吞咽过程中舌头的功能需要了解器官相对于外在结构的运动，以及与内壁结构和功能有关的基本关系。这些关系集中体现了一个更普遍的生理学原则，即舌头运动是由作用于肌细胞并由其产生的内力(收缩)和外力(粘连、机械拴系)的复杂平衡造成的。我们的方法根据语言的多尺度属性来考虑语言的力学和运动，并试图定义舌头精致复杂的组件阵列有助于在吞咽过程中协调和良好控制的力量产生的机制。为了实现这一目标，我们的实验室开发了新的技术，包括高分辨率磁共振成像，分析和表示肌丝和细胞力学的方法，以及能够量化空间尺度上的机械性能的计算框架。MRI以中尺度定义复杂的组织肌结构和力学，即中尺度的解剖结构(肌纤维束)，并为有限元多尺度舌功能分析提供解剖学和生物力学输入。我们推测，弥散加权MRI定义的中尺度肌纤维束排列决定了吞咽过程中协调力的产生和变形的模式。构成这些肌纤维束的材料和激活特性又主要来源于肌丝生物学和与潜在的骨骼肌细胞相关的关系。我们的研究将集中于语言功能的有限元模型的生成，并通过对其潜在的生物物理、机械和生理属性的不断发展的知识来充实。为了实现这一目标，我们提出了以下具体目标：目标1：建立一个结合细胞几何、细胞骨架结构和肌丝相互作用的舌骨骼肌收缩力生物物理模型。目的2：通过人体吞咽过程中多细胞肌纤维束的力学机制，推导排列的肌细胞的收缩能力与组织变形之间的三维关系。目的：根据骨骼肌功能的生物物理原理和磁共振成像的肌纤维束力学原理，建立吞咽过程中舌变形的有限元模型。基于本文提出的概念，从肌肉构筑和力学的定量测量角度来考虑吞咽过程中的舌力学应该是可行的。对与舌力产生相关的潜在机械机制的了解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问题。

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.