FastScan atomic force microscope for rapid imaging and property measurement of biological systems under natural conditions.

原子力显微镜（AFM）现在开始在生物学上发挥其潜力，使我们能够在自然（液体）环境中跟踪分子尺度上的生物动力学，监测驱动生物过程的力，并局部测量从亚蛋白水平到整个组织的机械特性。近年来，在谢菲尔德，我们率先使用这项技术来回答从光合膜中的蛋白质组织到细菌细胞壁结构的问题，我们正在扩展到全新的应用，例如测量单个植物细胞壁的局部机械特性，这对实现其功能很重要。然而，新一代原子力显微镜现在已经商业化，它提供的能力对于理解许多最紧迫的问题至关重要。在分子长度尺度上的处理本身是快速的，而AFM由于图像的每个像素是连续收集的，传统上具有有限的成像速率。新的快速扫描系统已经解决了这个问题，并且能够以亚秒的图像速率跟踪过程。类似地，单个蛋白质通常以非常小的力（在皮牛顿水平上）起作用，而细菌细胞壁等结构的性质在微小的纳米尺度上发生微妙的变化，这对它们的功能很重要。新的原子力显微镜能够使用更小的悬臂，比传统显微镜对力更敏感，对噪音更不敏感，使我们能够真正开始揭开生命系统的分子尺度特性。本项目的目的是购买一个快速扫描AFM系统，并使用它来解决各种各样的问题，包括生物太阳能收集，细菌细胞分裂，植物表皮细胞对环境变化的动态变化，以及膜蛋白功能。除了这些最初的应用之外，首席研究员在利用AFM解决生物学问题方面建立了成功的合作关系，并且新机器对于进一步扩展可以提出的问题至关重要。除此之外，新显微镜将成为谢菲尔德大学新中心的重要组成部分，该中心将汇集最先进的AFM技术，超分辨率光学和低温电子显微镜，结合国际领先的生物学，真正了解从单个分子到整个细胞和组织的生命系统。这一雄心壮志将在BBSRC资助的广泛研究组合中实现，为我们未来的成功提供基础设施，这对我们未来的成功至关重要。

Atomic force microscopy (AFM) is now starting to deliver its potential for biology, allowing us to follow biological dynamics at the molecular scale in their natural (liquid) environment, to monitor the forces that drive biological processes and locally measure mechanical properties from the sub-protein level to entire tissues. Over recent years in Sheffield we have pioneered the use of this technology to answer questions from protein organisation in photosynthetic membranes, to the architecture of bacterial cell walls and we are expanding into entirely new applications such as the measurement of local mechanical properties in the walls of individual plant cells that are important in enabling their function. However, a new generation of AFMs is now commercially available that provides capabilities that are vital for understanding many of the most pressing problems. Processes at molecular length scales are inherently fast, while AFM, because each pixel of an image is collected consecutively, has traditionally had limited imaging rate. The new fast scanning systems have tackled this problem and are able to follow processes with sub-second image rates. Similarly, single proteins typically operate with very small forces, at the picoNewton level, and the properties of structures such as bacterial cell walls vary subtly over tiny, nanometre, length scales in a way that is important for their function. The new AFMs are able to use smaller cantilevers that are inherently more sensitive to force and less susceptible to noise than those used in conventional microscopes, allowing us to really start to unravel the molecular scale properties of living systems. The purpose of this project is to purchase a fast scanning AFM system and to use it to tackle a diverse range of questions including biological solar energy harvesting, bacterial cell division, dynamic changes as plant epidermal cells respond to environmental changes, and membrane protein function. As well as these initial applications, the Principal Investigator has an excellent track record of building successful collaborations using AFM to tackle biological problems, and the new machine will be vital in further expanding the questions that can be broached. Beyond this, the new microscope will form a vital component of a new centre at the University of Sheffield that will bring together state-of-the-art techniques for AFM, super-resolution optics and cryo-electron microscopy, in combination with internationally leading biology, to really understand living systems from individual molecules to entire cells and tissue. This ambition will occur within an extensive portfolio of BBSRC funded research providing an underpinning facility, vital for our future success.