Imaging cellular function on the nanoscale

活细胞是基于分子和分子的组合相互作用，形成更复杂的结构，使细胞能够对环境的变化做出反应。为了了解活细胞是如何工作的，我们需要开发一种方法，以一种可控的方式启动这些过程，这样我们就可以用一种可以可视化关键成分的分辨率来跟踪发生的事情。由于细胞是柔软和敏感的，我们需要一种不涉及接触的方法来做到这一点，我们已经开发了一种利用纳米吸管对细胞表面成像的方法，纳米吸管通过尖端电流的减少来感知细胞表面。我们最近在成像细胞的方式上取得了突破，通过像缝纫机一样移动移液器在细胞表面移动，这使我们能够跳过细胞上非常常见的大特征。我们现在想利用这一进步，以一种可控的方式改变细胞，通过使细胞变形或传递分子来启动细胞内的信号，从而能够开始将细胞结构与其功能联系起来。我们将开发一种方法来绘制和表征细胞表面的一些关键结构和分子。首先在模型样本上开发和完善这些方法后，我们将把它们应用于活细胞，以证明具有非常高空间分辨率的成像功能现在是可能的。

Livings cells are based on molecules and assemblies of molecules interacting with each other to form more complex structures and to enable the cell to respond to changes in its environment. To understand how living cells work we need to develop method to initiate these process in a controlled way so we can then follow what happens with a resolution that can visualise the key components.Since cells are soft and responsive one needs a way to do this which does not involve contact and we have developed a method of imaging the cell surface using a nanopipette which senses the cell surface by the reduction in current flowing through its tip. We have recently made a breakthrough in the way we image cells by moving the pipette like a sewing machine over the surface, which allows us to jump over large features which are very common on cells. We now want to exploit this advance to be able to also alter the cell in a controlled way, by either deforming the cell or delivering molecules that will initiate signals inside the cell, to be able to start to relate the cell structure to its function. We will develop a method to map and characterise some of the key structures and molecules on the cell surface. After firstly developing and refining these method on model samples we will then apply them to live cells to demonstrate that imaging function with very high spatial resolution is now possible.