COBRE: UNV MED SCH: P3: PROTEOMICS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 项目3：对平滑肌细胞进行微调，以执行它们周围许多不同器官和血管系统特有的机械功能。例如，血管平滑肌的特定张力控制血压，而呼吸道平滑肌的缩短则调节以优化呼吸。平滑肌细胞收缩状态的改变是导致高血压导致心力衰竭和哮喘相关的气道高反应性等病理生理状态的近端原因，这些疾病的发病机制涉及到对平滑肌收缩和信号成分之间的延长反馈做出反应的平滑肌重塑。然而，在平滑肌重塑和疾病的模型中，收缩成分仍然是一个黑匣子，部分原因是人们还没有很好地了解平滑肌收缩的分子细节，以及力产生和力感知机制之间的相互作用。平滑肌通过肌动蛋白-肌球蛋白ATPase反应产生力量和运动。但是，除了产生力量和运动之外，平滑肌肌球蛋白还感知力，根据所产生的力改变其生化动力学。肌球蛋白？S的力产生和力感觉机制之间的相互作用被认为在调节平滑肌的力学特性中起着关键作用，并与通常被称为闩锁的经济紧张性收缩有关。然而，一个肌球蛋白分子产生的力是如何传递的，并协同影响邻近肌球蛋白分子在平滑肌中的生化动力学，人们对此知之甚少。该项目的目标是使用最先进的荧光显微镜和激光陷阱来表征平滑肌肌球蛋白-S力生成和力传感机制之间的相互作用，作为确定正常和过度收缩状态下平滑肌独特机械特性的分子基础的先决条件。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project 3: Smooth muscle cells are finely tuned to carry out mechanical functions specific to the many different organs and vasculature they surround. For instance, the specific tone of vascular smooth muscle controls blood pressure whereas the shortening of airway smooth muscle is tuned to optimize respiration. Altered contractile states of smooth muscle cells are the proximal cause of pathophysiological states such as hypertension resulting in cardiac failure and airway hyperresponsiveness associated with asthma, and the pathogenesis of these diseases involves smooth muscle remodeling in response to extended feedback between the contractile and signaling components of smooth muscle. Yet the contractile component remains something of a black box in models of smooth muscle remodeling and disease, in part because the molecular details of smooth muscle contraction and the interplay between force-generating and force-sensing mechanisms are not well understood. Smooth muscle generates force and movement through the smooth muscle actin-myosin ATPase reaction. But in addition to generating force and movement, smooth muscle myosins also sense force, modifying their biochemical kinetics in response to the forces they generate. The interplay between smooth muscle myosin?s force-generating and force-sensing mechanisms is thought to play a critical role in tuning the mechanical properties of smooth muscle and has been implicated in the economic tonic contractions of smooth muscle often referred to as latch. Yet remarkably little is known about how the forces generated by one myosin molecule are transmitted and cooperatively affect the biochemical kinetics of neighboring myosin molecules in smooth muscle. The goal of this project is to use state-of-the-art fluorescence microscopy and laser traps to characterize the interplay between smooth muscle myosin?s force-generating and force-sensing mechanisms as a prerequisite for determining the molecular basis for the unique mechanical properties of smooth muscle in normal and hypercontractile states.