Development of a novel micropipette aspiration-based force sensing technique to measure single cell sliding friction

Abstract

In numerous biological scenarios the motion of cells is tangential to the surface of contact such as in extravasation of leucocytes, blood flow regulation, and cell migration. In these cases, adhesion molecules on the cells form bonds with the substrate upon contact and when the cells propagate, the bonds are ruptured at an angle sustained by the cells’ curvature. The presence of tangential force component (or the sliding friction) and the recruitments of auxiliary stress-dependent ligands at the adhesion site mean conventional cell detachment model is not adequate to explain the rupture mechanics of a sliding cell. Thus, we propose an instrument based on the micropipette aspiration technique to solve this problem. In this setup, a highly sensitive friction force sensor is made out of a long, thin, and hollow micropipette that deflects as a function of the tangential force experienced by a cell, aspirated at the tip, when rubbed against a moving substrate. Similarly, the substrate is connected to a normal force sensor that detects the perpendicular force acting on the cell by the surface during sliding. This dual force sensors setup allows direct measurements of all forces experienced by the moving cell to be gathered in real time. Separation between force sensors that monitors the friction and the normal force also allows the sensitivities of the sensors to be tuned independently. To prove the reliability of this device, we analyse the sliding of a glass bead against three different surface materials across multiple initial normal force values. Experiments are also performed across various sliding speeds and directionalities.The effect of varying load, speed and directionality are compared to similar meso- and nanoscale experiments and discussed. It is discovered that micro-friction has dependency on asperity properties that are intermediary to meso- and nanoscale experiments. Following that, experiments are performed with red blood cells, to demonstrate the first attempt of the device to measure bio-friction at single cell level. To supplement the sliding results, tactile experiment where the cells are detached perpendicular to the surface is carried out, and the rupture force is compared to that during sliding. It is found that the rupture force is indeed smaller in the presence of tangential force (during sliding). This provide novel experimental insight into quantitative values of bond-tilted rupture mechanics that can potentially be adopted in developing models that are more realistic and biologically relevant to cell detachment and bond rupture.