Exploring new frontiers in mechanical characterization of cells: membrane tether extraction with optical tweezers and implications for healthy and sickle red blood cells.

Human cells are complex units due to their internal organization and also based on how they interact with other cells and the extracellular environment. Such interactions depend not only on the biochemical but also on the mechanical properties of the cell surface. In erythrocytes, the cell surface plays a key role, not only ensuring efficient oxygen distribution but also being deformed to squeeze through blood capillaries to perfuse tissues, and regaining its shape upon exiting these tiny vessels. In this study, we developed an innovative method based on the extraction of membrane tethers from the surface of red blood cells using optical tweezers. The method allows to efficiently characterize the biomechanical properties of red blood cells. We show that, in sickle cell disease, the cell membrane becomes stiffer over time and that membrane friction increases with tether length. We fitted these responses to a phenomenological model that extracts quantitative parameters characterizing cell mechanics. The results demonstrate that our method can generate a viable diagnostic potential, using mechanobiological features of erythrocytes with possible applications in various experimental and clinical situations.