Rigidity sensing by blood-borne leukocytes: Is it independent of internal signaling?

Abstract

<abstract> <p>Atherosclerosis is a chronic inflammatory disease that results in the formation of lipid-rich lesions and stiffening of arterial walls. An increasing body of evidence suggests that nearly all members of the leukocyte family accumulate within atherosclerosis-prone arteries and participate in various stages of disease progression. Recently, it has been proposed that progressive changes of the elastic modulus of the arterial wall during plaque development may directly influence the kinematics of leukocyte rolling. In the present study, we propose that rigidity sensing of rolling leukocytes may occur spontaneously due to the stiffness-dependent elastic instability of reversible bonds between rolling leukocytes and the arterial walls. This effect is mechanistic in nature and operates independently of cell biochemical signaling. To partially test this hypothesis, we measured the rolling velocities of functionalized microparticles, comparable in size to leukocytes, interacting with E-selectin coated substrates of controlled stiffness. The kinematic analysis of the particles' motion reveals a larger rolling velocity on softer substrates, aligning with previous reports regarding monocytes. A simple kinetic model for a cluster of reversible bonds formed between a cell and the underlying substrate demonstrates that the critical forces needed for bond disassembly decrease as substrate stiffness decreases. Consequently, bonds are more likely to break on softer substrates, resulting in enhanced cell mobility.</p> </abstract>