Understanding how cells interact with their environment provides crucial insights into cell biology and has wider implications in medicine, including disease diagnosis and cancer therapy. So far, a variety of tools – the most popular being traction force microscopy (TFM) – have been developed to study the interplay between cells and their 3D microenvironment. However, they are limited in their ability to provide comprehensive information on degrees of freedom like rotational motion, which remains speculative as a result of technical constraints and limited research on the topic.
Thus, engineering experts at the University of Hong Kong have proposed a novel technique to measure the cell traction force field and tackle the research gap.
The interdisciplinary research team, led by Dr Zhiqin Chu of the Department of Electrical and Electronic Engineering and Dr Yuan Lin of the Department of Mechanical Engineering, used a single nitrogen-vacancy (NV) centres in nanodiamonds (NDs) to propose a linear polarisation modulation (LPM) method which can measure both, the rotational and translational movement of markers on cell substrates.
The study offers a new perspective on the measurement of multi-dimensional cell traction force field and the results have been published in the journal Nano Letters. The research, entitled ‘All-Optical Modulation of Single Defects in Nanodiamonds: Revealing Rotational and Translational Motions in Cell Traction Force Fields’, is also featured as the supplementary cover of the journal.
The research showed high-precision measurements of rotational and translational motion of the markers on the cell substrate surface. These experimental results corroborate the theoretical calculations and previous results.
Given their ultrahigh photostability, good biocompatibility, and convenient surface chemical modification, fluorescent NDs with NV centres are excellent fluorescent markers for many biological applications. The researchers found that based on the measurement results of the relationship between the fluorescence intensity and the orientation of a single NV centre to laser polarisation direction, high-precision orientation measurements and background-free imaging could be achieved.
Thus, the team’s LPM method helps solve technical bottlenecks in cellular force measurement in mechanobiology, which encompasses interdisciplinary collaborations from biology, engineering, chemistry and physics.
Dr Chu noted that most cells in multicellular organisms experience forces that are highly orchestrated in space and time. The development of multi-dimensional cell traction force field microscopy has been one of the greatest challenges in the field.
Compared to the conventional TFM, this new technology offers a new and convenient tool to investigate the real 3D cell-extracellular matrix interaction. It helps achieve both rotation-translational movement measurements in the cellular traction field and reveals information about the cell traction force.
The main highlight of the research is the technology’s ability to indicate both the translational and rotational motion of markers with high precision. It is a big step towards analysing mechanical interactions at the cell-matrix interface. It also offers new avenues of research.
Through specialised chemicals on the cell surface, cells interact and connect as part of a process called cell adhesion. The way a cell generates tension during adhesion has been primarily described as ‘in-plane.’ Processes such as traction stress, actin flow, and adhesion growth are all connected and show complex directional dynamics.
The LPM method could help make sense of the complicated torques surrounding focal adhesion and separate different mechanical loads at a nanoscale level (e.g., normal tractions, shear forces). It may also help understand how cell adhesion responds to different types of stress and how these mediate mechanotransduction (the mechanism through which cells convert mechanical stimulus into electrochemical activity).
This technology is also promising for the study of various other biomechanical processes, including immune cell activation, tissue formation, and the replication and invasion of cancer cells. For example, T-cell receptors, which play a central role in immune responses to cancer, can generate extremely dynamic forces vital to tissue growth. This high-precision LPM technology may help analyse these multidimensional force dynamics and give insights into tissue development.
The research team is actively researching methodologies to expand optical imaging capabilities and simultaneously map multiple nanodiamonds.
