Imaging cellular function on the nanoscale

纳米尺度的细胞功能成像

• 批准号: EP/H01098X/1
• 负责人: David Klenerman
• 金额: $ 43.99万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FH01098X%2F1
• 关键词: Imaging; cellular; function; nanoscale

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.

活细胞是基于相互作用的分子和分子的集合，以形成更复杂的结构，并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，以一种受控的方式启动这些过程，这样我们就可以跟踪关键成分的分辨率发生了什么。由于细胞很软，而且反应灵敏，人们需要一种不涉及接触的方法来做到这一点，我们开发了一种使用纳米管对细胞表面进行成像的方法，该方法通过流经细胞尖端的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，通过像缝纫机一样在表面上移动吸管，这使得我们能够跳过细胞上非常常见的大型特征。我们现在想要利用这一进步，能够以一种受控的方式改变细胞，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改进这些方法，然后将它们应用于活细胞，以证明现在可以实现非常高空间分辨率的成像功能。

项目成果

Low Stress Ion Conductance Microscopy of Sub-Cellular Stiffness.

• DOI: 10.1039/c6sm01106c
• 发表时间: 2016-10-14
• 期刊: Soft matter
• 影响因子: 3.4
• 作者: Clarke RW;Novak P;Zhukov A;Tyler EJ;Cano-Jaimez M;Drews A;Richards O;Volynski K;Bishop C;Klenerman D
• 通讯作者: Klenerman D

A hybrid scanning mode for fast scanning ion conductance microscopy (SICM) imaging.

• DOI: 10.1016/j.ultramic.2012.06.015
• 发表时间: 2012-10
• 期刊: ULTRAMICROSCOPY
• 影响因子: 2.2
• 作者: Zhukov, Alex;Richards, Owen;Ostanin, Victor;Korchev, Yuri;Klenerman, David
• 通讯作者: Klenerman, David