Profiling of time-dependent human plasma protein adsorption on non-coated and heparin-coated oxygenator membranes.

Patients with severe lung diseases are highly dependent on lung support systems. Despite many improvements, long-term use is not possible, mainly because of the strong body defence reactions (e.g. coagulation, complement system, inflammation and cell activation). The systematic characterization of adsorbed proteins on the gas exchange membrane of the lung system over time can provide insights into the course of various defence reactions and identify possible targets for surface modifications. Using comprehensive mass spectrometry analyses of desorbed proteins, we were able to identify for the first time binding profiles of over 500 proteins over a period of six hours on non-coated and heparin-coated PMP hollow fiber membranes. We observed a higher degree of remodeling of the protein layer on the non-coated membrane than on the coated membrane. In general, there was a higher protein binding on the coated membrane with exception of proteins with a heparin-binding site. Focusing on the most important pathways showed that almost all coagulation factors bound in higher amounts to the non-coated membranes. Furthermore, we could show that the initiator proteins of the complement system bound stronger to the heparinized membranes, but the subsequently activated proteins bound stronger to the non-coated membranes, thus complement activation on heparinized surfaces is mainly due to the alternative complement pathway. Our results provide a comprehensive insight into plasma protein adsorption on oxygenator membranes over time and point to new ways to better understand the processes on the membranes and to develop new specific surface modifications.