Muscle anisotropy of the respiratory pump

本研究的中心假设是，正常的横膈膜肌肉组织是各向异性的（横向比纵向更硬），这种结构：(a)由desmin中间纤维介导，(b)对横膈膜的正常节能功能很重要。此外，地精蛋白可能有助于肌肉细胞区分和响应不同的纵向和横向应变。这些问题将通过分析正常和desmin敲除组织来回答。该项目旨在了解定向组织中的细胞骨架元件和机械转导信号机制如何引起肌肉组织中机械特性和机械反应的各向异性。这些都是重要的基础研究，将对肌肉骨骼组织如何组织和调整以感知和响应其机械环境具有广泛的意义。提出的研究包括两个重点：实验力学和分子细胞生物学。该研究包括几个创新方面，如在隔膜组织中应用更多的生理、双轴负荷，并提出呼吸泵定向机械转导的想法。本研究将促进对呼吸泵功能和定向机械转导的认识。该项目整合了微观力学、机械转导和呼吸生理学等领域。此外，该项目将加强对研究生、医学生的培训，并通过一个暑期项目（SMART）对生物工程研究感兴趣的本科生。这些受训者中肯定会有一些来自代表性不足的少数民族。

CBET-0650686 Boriek The central hypothesis of this research is that normal diaphragm muscle tissue is anisotropic (stiffer in transverse than longitudinal direction) and this structure is: (a) mediated by desmin intermediate filaments, and (b) important to normal energy-efficient function of the diaphragm. Further, desmin may help the muscle cells to distinguish and respond differently to longitudinal and transverse strains. These questions will be answered by analyzing both normal and desmin knock-out tissue. This project seeks to understand how cytoskeletal elements and mechanotransductive signaling mechanisms in oriented tissues give rise to anisotropy of both mechanical properties and mechanical responses in muscle tissue. These are important fundamental studies that will have broad implication on how musculoskeletal tissues are organized and tuned to sense and respond to their mechanical environment. The proposed studies involve two thrusts: experimental mechanics, and molecular cell biology. The proposed research includes several innovative aspects such as applying more physiologic, biaxial loading to diaphragm tissue and proposing the idea of directional mechanotransduction in the respiratory pump. This research will advance the understanding of respiratory pump function as well as directional mechanotransduction. The project integrates the fields of micromechanics, mechanotransduction, and respiratory physiology. In addition, this project will enhance training of graduate students, medical students, and through a summer program (SMART) undergraduate students interested in bioengineering research. Some of these trainees will certainly be drawn from the underrepresented minority population.