Regulation of Focal Adhesion Initiation by Lipids and Membrane Bending

该奖项的研究目标是了解细胞如何粘附在天然细胞外基质和生物材料中使用的人工表面等表面的早期部分。具体来说，这项研究将探讨膜如何控制脂质的运输和重要的粘附分子粘附斑块的招聘。这些实验将使用先进的显微镜，能够测量这些结构中的细胞粘附动力学和分子动力学。如果成功，这些测量将导致更好地了解细胞粘附动力学，以及为什么动脉粥样硬化病变形成在低和振荡流体剪切应力的区域，如在血管分叉和支架附近。它对剪切诱导的血管舒张也可能很重要，已知剪切诱导的血管舒张可以抵消小动脉中压力诱导的肌源性收缩，因此是血压控制和高血压的重要组成部分。 如果成功的话，这些研究将显著增加该领域对机械传感的理解，特别是对质膜的分子尺度功能组织的理解。 这种理解可能有助于未来的机械感觉理论的测试和新的生物力学模拟物的发展，如单层囊泡与蛋白质，蛋白聚糖和细胞骨架。 由于几乎所有的细胞都需要感知和施加力，这些研究可能对许多机械生物学过程具有广泛的意义，包括骨重建，干细胞分化和发育生物学。膜机械生物学的拟议研究将被纳入研究生培训和本科生荣誉论文的准备。这项培训将成为年轻科学家（6-12年级）的基础，通过现代三维可视化使分子尺度的机械生物学更容易获得。这种外联活动将提供机会，接触代表性不足的群体，如妇女和少数民族以及宾夕法尼亚州农村的学生，他们在考虑高等教育选择时经常访问宾夕法尼亚州立大学。

The research objective of this award is to understand the very early parts of how cells adhere to surfaces such as natural extracellular matrices and artificial surfaces used in biomaterials. Specifically, this research will investigate how the membrane controls the transport of lipids and the recruitment of important adhesion molecules to adhesion plaques. These experiments will use advanced microscopes capable of measuring dynamics of cellular adhesions and molecular dynamics in these structures. If successful, these measurements would lead to a better understanding of cellular adhesion dynamics and why atherosclerotic lesions form in areas of low and oscillating fluid shear stress such as at blood vessel bifurcations and near stents. It may also be important for shear-induced vasodilation, which is known to counteract pressure-induced myogenic constriction in small arteries and thus is an important component of blood pressure control and hypertension. If successful, these studies would add significantly to the field's understanding of mechanosensing in particular and molecular scale functional organization of plasma membranes in general. This understanding may assist in future testing of mechanosensation theories and in the development of new biomechanical mimetics, such as unilamellar vesicles with proteins, proteoglycans, and cytoskeleton. Since almost all cells need to sense and apply force, these studies may have broad implications for many mechanobiological processes including bone remodeling, stem cell differentiation, and developmental biology. The proposed research on membrane mechanobiology will be integrated into graduate training and in undergraduate honors thesis preparation. This training will form the basis of outreach to young scientists (grades 6-12) in which molecular scale mechanobiology is made more accessible through modern 3-D visualization. Such outreach will provide opportunities to reach underrepresented groups such as women and minorities and students in rural Pennsylvania, who visit Penn State frequently as they consider their higher education options.