Optical Tweezers in Probing the Collagen Matrix Viscoelasticity
Optical Tweezers method is a powerful tool to probe the collagen matrix viscoelasticity. The increase in matrix viscoelasticity may indicate the potential tissue injury.
Tissue injury can lead to a fibrotic disease, for example lethal cirrhosis in the liver. In the cirrhotic stage, the disease is difficult to cure because of the excessive production of scar tissue caused by elevated crosslinking of extracellular matrix (ECM). So far, the clinical trials targeting the most widely reported ECM crosslinking mechanism of liver cirrhosis namely lysyl oxidase (LOX) unfortunately show no efficacy. This raises the question whether there is another, more significant contributor to the crosslinking of ECM in the disease.
In a study conducted at Tsinghua University, researchers discovered that the extracellular matrix (ECM) is highly cross-linked in the cirrhotic liver tissue. Furthermore, they showed that the advanced glycation end-products (AGEs) are also responsible for the high level of crosslinking. Surprisingly, AGE-mediated crosslinking showed the highest increase in disease progression compared to LOX and transglutaminase (TGM) mediated cross-linking. By using the MMI CellManipulator Optical Tweezers, researchers could probe the viscoelasticity of the collagen matrix. In-vitro results show that AGE-crosslinked collagen expressed an increase in stiffness (elasticity) compared to the non-crosslinked matrix. The stress relaxation time (viscosity) also shows a similar trend. It implies that the AGE-crosslinked collagen is more difficult to remodel by the tissue.
The impact of AGE-mediated crosslinking in the progression of cirrhosis was unknown before. This new finding definitely broadens our horizon about the role of cellular mechanosensing in disease progression and surely advances the way to combat the disease.
