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附着在生物材料中使用的天然细胞外基质和人造表面等表面的非常早期的部分。具体地说，这项研究将调查膜如何控制脂质的运输和重要黏附分子对黏附斑块的募集。这些实验将使用先进的显微镜，能够测量细胞黏附的动力学和这些结构中的分子动力学。如果成功，这些测量将导致更好地了解细胞黏附动力学，以及为什么动脉粥样硬化病变形成在低和振荡的流体剪应力区域，如血管分叉处和支架附近。它对切变诱导的血管扩张也可能很重要，众所周知，切变诱导的血管扩张可以对抗压力引起的小动脉肌源性收缩，因此是血压控制和高血压的重要组成部分。如果成功，这些研究将大大增加该领域对机械传感的了解，特别是对质膜的分子尺度功能组织的总体理解。这一理解可能有助于未来对机械感觉理论的测试和新的生物力学模拟的发展，如含有蛋白质的单层囊泡、蛋白多糖和细胞骨架。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，包括骨重塑、干细胞分化和发育生物学。拟议的膜机械生物学研究将被整合到研究生培训和本科生荣誉论文准备中。这一培训将成为接触年轻科学家(6-12年级)的基础，通过现代3-D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到代表人数不足的群体，如妇女和少数群体以及宾夕法尼亚州农村的学生，他们在考虑自己的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.