It is reported that mechanics plays an important role in cell biology. Cells harness these mechanical forces to explore their environment and perceive the behavior of living cells around them. The physical properties of the cell environment in turn affect cell function. Therefore, understanding how cells interact with the environment provides important insights for cell biology and has a broader impact in medicine, including disease diagnosis and cancer treatment.
Graphic summary. Source: DOI: 10.1021/acs.nanolet.2c02232
So far, researchers have developed many tools to study the interaction between cells and their 3D microenvironment. One of the most popular technologies is traction microscope (TFM). It is the main method to determine the traction force on the surface of cell matrix, and provides important information about how cells perceive, adapt and respond.
However, the application of full focus mode (TFM) is limited to providing information about the translational movement of markers on the cell matrix. Due to technical limitations and limited research on the subject, information about other degrees of freedom (such as rotational motion) is still speculative.
Engineering experts from the University of Hong Kong proposed a new technology to measure the cell traction field and solve the research gap. The interdisciplinary research team is led by Dr. Zhu Zhiqin from the Department of Electrical and Electronic Engineering and Dr. Yuan Lin from the Department of Mechanical Engineering. They proposed a linear polarization modulation (LPM) method using a single nitrogen vacancy (NV) center in nano diamonds (NDs), which can measure the rotation and translation of markers on the cell matrix.
Source: Nano Letters
This research provides a new perspective for the measurement of multi-dimensional cell traction field, and its results have been published in the journal Nano Letters.
The research shows that the rotation and translation of markers on the surface of cell matrix are measured with high precision. These experimental results confirm the theoretical calculations and previous results.
Fluorescent ND with NV center is an excellent fluorescent marker for many biological applications due to its high photostability, good biocompatibility and convenient surface chemical modification. Researchers found that based on the measurement results of the relationship between the fluorescence intensity of a single NV center and the laser polarization direction, high-precision directional measurement and background free imaging can be achieved.
Source: Nano Letters
Therefore, the LPM method invented by the team is helpful to solve the technical bottleneck of cell force measurement in mechanical biology, including interdisciplinary cooperation in biology, engineering, chemistry and physics.
"Most cells in multicellular organisms have experienced a highly coordinated force between space and time. The development of multi-dimensional cell traction field microscope has always been one of the biggest challenges in this field." Dr. Zhu said.
Source: Nano Letters
The main highlight of this study is that it can accurately indicate the translation and rotation of markers. This is a major step in the analysis of mechanical interactions at the cell matrix interface. It also provides new research approaches.
Through special chemicals on the surface of cells, cells interact and connect as part of a process called cell adhesion. The way cells generate tension during adhesion is mainly described as "in plane". The processes of traction stress, actin flow and adhesion growth are all interrelated and show complex directional dynamics.
The LPM method can help to understand the complex torque attached around the focus and separate different mechanical loads (e.g., normal traction, shear) at the nanoscale. It may also help to understand how cell adhesion responds to different types of pressures and how these pressures mediate mechanical transduction (the mechanism by which cells convert mechanical stimuli into electrochemical activities).
This technique is also expected to be used to study various other biomechanical processes, including immune cell activation, tissue formation, and cancer cell replication and invasion. For example, T cell receptors, which play a central role in the immune response to cancer, can generate extremely dynamic forces that are critical to tissue growth. This high-precision LPM technique may be helpful to analyze these multi-dimensional force dynamics and to understand tissue development in depth.
The research team is actively researching methods to expand optical imaging capabilities and simultaneously paint multiple nano diamonds.
Source:All-Optical Modulation of Single Defects in Nanodiamonds: Revealing Rotational and Translational Motions in Cell Traction Force Fields, Nano Letters (2022). DOI: 10.1021/acs.nanolett.2c02232