Muscle anisotropy of the respiratory pump

CBET-0650686 Boriek本研究的中心假设是正常的膈肌组织是各向异性的（横向比纵向更硬），并且该结构：（a）由结蛋白中间丝介导，以及（B）对膈肌的正常能量有效功能很重要。此外，结蛋白可以帮助肌细胞区分纵向和横向应变并作出不同的反应。这些问题将通过分析正常和结蛋白敲除组织来回答。该项目旨在了解定向组织中的细胞骨架元件和机械传导信号机制如何引起肌肉组织中机械特性和机械响应的各向异性。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产生广泛的影响。拟议中的研究涉及两个方面：实验力学和分子细胞生物学。该研究包括几个创新方面，如应用更多的生理，双轴载荷的隔膜组织和提出的想法，定向机械转导的呼吸泵。这项研究将促进对呼吸泵功能以及定向机械转导的理解。 该项目整合了微观力学，机械传导和呼吸生理学领域。此外，该项目还将加强对研究生、医学生和对生物工程研究感兴趣的本科生的暑期项目（SMART）培训。其中一些受训人员肯定会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.