Periodic Reporting for period 2 - MechaDynA (Multi-scale mechanics of dynamic leukocyte adhesion)
Reporting period: 2020-03-01 to 2021-08-31
One of the first steps in immune response involves the slowdown of white blood cells flowing with the blood stream for then firmly adhere to the vascular wall and crawl to reach the site of injury or inflammation. During this process, the blood flow and active force generation by the cells result in important mechanical forces that deform the cells and break individual adhesion linkages between them. These forces are generated at different time scales, from very short to very long lapses of time. Thus, knowing the forces involved during the different steps is essential to better understand this process. However, measurement of forces on cells at the small length scales of the cell and covering all the range of time scales requires development of new nanotools: instruments working at the nanometer scale. The aim of this project is to develop new nanotools to understand the physics behind white blood cells activity. The outcomes will establish novel nanotools applicable to understand other essential processes such as virus-cell binding. Moreover, it will provide fundamental understanding of the immune response, which may lead to better diagnosis and treatment of disease.
A team of experts in the fields of biophysics, engineering, nanotechnology and computational biology has been formed. Two new nanotools have been implemented: 1) high-speed atomic force microscopy (HS-AFM) that gives access force events at the shortest timescales, and 2) acoustic force spectroscopy (AFS) that gives access to biomechanical processes at long timescales. The new nanotools have been tested on model systems and have been adapted and improved to work on living cells. Experiments on living cells have been carried out. We have published two methodological works on AFM calibration methods, necessary for robust and quantitative measurements. Two review articles on HS-AFM have been published.
This project will establish two new nanotools to study the mechanics of living cells at unprecedented timescales. This will allow understanding fundamental biophysical processes that occur in very short and very long times, so far unexplored. The development of the nanotools may lead to patents and their application to study other biological and physical systems, such as virus-cell binding. The expected results will provide information from a novel perspective on essential steps during immune response, important for better diagnosis, prognosis and treatment of disease.