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. Author manuscript; available in PMC: 2020 Oct 28.
Published in final edited form as: Nat Immunol. 2019 Sep 18;20(10):1269–1278. doi: 10.1038/s41590-019-0491-1

Fig. 1 |. Immune cells are subjected to external forces from, and apply endogenous forces to, their surroundings, which can be measured by biophysical techniques.

Fig. 1 |

a, A lymphocyte rolling on the endothelium experiences forces. Blood flow applies a tangential force Fs to the cell center and a rotational torque Ts, which are supported by the tether force Ft at the rear with an inclined angle. The tangential component Ftx balances Fs. The normal component Fty generates a torque Fty × r × sinθ to balance Ts and the torque of the tangential force Ftx × r × cosθ. Fty also induces a reaction Fc from the endothelium. b,c, During migration (b) and formation of the immunological synapse (c), a lymphocyte can apply endogenous forces, generated by actomyosin contraction and actin retrograde flow, on the ECM (b) or the APC (c). d, The TCR and CD8, localized at the tip of the microvillus of a T cell interacting with an APC, bind pMHC in the center, while LFA-1 binds to ICAM-1 at the periphery. CD45 is uniformly distributed. eg, TFM (e), mPADs (f) and molecular tension probes (g) measure the endogenous force generated by cells and applied on receptors. Force is measured from the displacements of beads embedded in an elastic substrate to which the cell adheres (TFM), the deflections of elastic pillars to which the cell attaches (mPAD) and the unquenched fluorescence (molecular tension probe). Cellular-level forces on many receptors are measured by TFM and mPAD, which reflect only the tangential force components, because only lateral bead displacements and pillar deflections can be visualized by the microscope’s top view. By comparison, molecular tension probes measure tension along the long axis of the receptors. h, Tension gauge tethers fail when force exceeds a designed threshold, which thus limits the level of tension that the cell can apply on its receptors.