Biomimetic Interfaces Reveal Activation Dynamics of C‐Reactive Protein in Local Microenvironments

Abstract

CRP is an acute-phase reactant secreted by hepatocytes in the liver upon stimulation with endogenous proinfl ammatory cytokines and reaches a level, 100–1000-fold compared to normal conditions (0.8 mg L −1 ) in blood. [ 1 ] CRP levels are clinically measured to monitor the severity of infection, infl ammatory conditions, and cardiovascular diseases. Circulating CRP specifi cally binds to phospholipids as well as immunoglobulins in damaged tissue, [ 2 ] which enhances innate immune responses by recruiting complement components. Generally, CRP forms a pentraxin (115 kDa), a non-covalent symmetrical arrangement of fi ve identical subunits (23 kDa). [ 3 ] Each subunit possesses a PC-binding site coordinated by two calcium ions. The binding of CRP to PCs as a molecular interaction mechanism for activating CRP at the site of infection is intriguing. Classically, two Ca 2+ are believed to have a common equilibrium dissociation constant ( K D = 0.06 × 10 −3 M ) to the PC-binding pocket in CRP. [ 4 ] Recent advances revealed an intricate profi le of the CRP–Ca 2+ affi nities in which each Ca 2+ is taken up in a stepwise manner ( K D,high = 0.03 × 10 −3 M , K D,low = 5.45 × 10 −3 M ). [ 5 ]