One of the principal responses of the immune system when confronting damage, inflammation, is the body’s first attempt to remove harmful stimuli and start the restoration process. When inflammation begins, there is an important migration of white cells to the localized point of action. These cells, the same as any other cell in movement, adapt their morphology and migration speed in response to intrinsic and extrinsic cues.
Spurred on by their interest in the movements of these cells, a multidisciplinary team at the University of California, San Diego studied this property using Fourier traction force microscopy, measuring the spatiotemporal evolution of shape and the traction stress and tension. The results of the study offer insights into eventually improving treatment for chronic inflammatory diseases such as arthritis, irritable bowel syndrome, Type 1 diabetes, and multiple sclerosis.
One of the team members, Juan C. Lasheras, a professor in the department of Mechanical and Aerospace Engineering and Bioengineering, and in the Institute for Engineering in Medicine, said, “Understanding the way in which these cells generate the necessary forces to move from the blood stream to the site of inflammation will guide the design of new strategies that could target specific mechanical processes to control their migration.”
Due to the complexity of the task, there were different approaches required, involving engineering and biological sciences. The researchers analyzed two mutant strains of Dictyostelium discoideum on normal and highly adhesive substrates. Due to the different dynamics, the study suggested that the two strains use distinct mechanisms, leading the study to confirm that distinct-acting cross-linkers present different mechanisms to achieve migration.
The study was able to show that “wild-type cells migrate in a step-wise fashion, mainly forming stationary traction adhesions along their anterior–posterior axes and exerting strong contractile axial forces,” according to an article in MedScape.
“This work was made possible through interdisciplinary approaches that applied mathematical tools to a basic question in cell biology about how cells move,” stated Richard Firtel, a researcher involved in the study. “We were able to discover the basic mechanisms that control amoeboid movement, which we then applied to understanding white blood cells.” Currently, the team is working to extend their technical skills to study leukocytes and investigate if the related migration and invasion of cancerous cells are related.
Considering that diseases such as IBD and multiple sclerosis are marked by high levels of inflammation in the body, understanding the cellular mechanisms behind inflammation offering promise for craft an entirely new set of therapies that could dramatically impact quality of life for those who suffer with these diseases.