@misc{lee_substrateenzyme_affinitybased_2020, 
author={Lee, S., Ganesan, R., Krüger-Genge, A., Kratz, K., Franke, R., Lendlein, A., Jung, F.},
title={Substrate-enzyme affinity-based surface modification strategy for endothelial cell-specific binding under shear stress},
year={2020},
howpublished = {journal article},
doi = {https://doi.org/10.3233/CH-190736},
abstract = {Establishing an endothelial cell (EC) monolayer on top of the blood contacting surface of grafts is considered to be a promising approach for creating a hemocompatible surface. Here we utilized the high affinity interactions between the EC plasma membrane expressed enzyme called endothelin converting enzyme-1 (ECE-1) and its corresponding substrate big Endothelin-1 (bigET-1) to engineer an EC-specific binding surface. Since enzymatic cleavage of substrates require physical interaction between the enzyme and its corresponding substrate, it was hypothesized that a surface with chemically immobilized synthetic bigET-1 will preferentially attract ECs over other types of cells found in vascular system such as vascular smooth muscle cells (VSMCs). First, the expression of ECE-1 was significantly higher in ECs, and ECs processed synthetic bigET-1 to produce ET-1 in a cell number-dependent manner. Such interaction between ECs and synthetic bigET-1 was also detectible in blood. Next, vinyl-terminated self-assembled monolayers (SAMs) were established, oxidized and activated on a glass substrate as a model to immobilize synthetic bigET-1 via amide bonds. The ECs cultured on the synthetic bigET-1-immobilized surface processed larger amount of synthetic bigET-1 to produce ET-1 compared to VSMCs (102.9±5.13 vs. 9.75±0.74 pg/ml). The number of ECs bound to the synthetic bigET-1-immobilized surface during 1 h of shearing (5dyne/cm2) was approximately 3-fold higher than that of VSMCs (46.25±12.61 vs. 15.25±3.69 cells/100×HPF). EC-specific binding of synthetic bigET-1-immobilized surface over a surface modified with collagen, a common substance for cell adhesion, was also observed. The present study demonstrated that using the substrate-enzyme affinity (SEA) of cell type-specific enzyme and its corresponding substrate can be an effective method to engineer a surface preferentially binds specific type of cells. This novel strategy might open a new route toward rapid endothelialization under dynamic conditions supporting the long-term patency of cardiovascular implants.},
note = {Online available at: \url{https://doi.org/10.3233/CH-190736} (DOI). Lee, S.; Ganesan, R.; Krüger-Genge, A.; Kratz, K.; Franke, R.; Lendlein, A.; Jung, F.: Substrate-enzyme affinity-based surface modification strategy for endothelial cell-specific binding under shear stress. Clinical Hemorheology and Microcirculation. 2020. vol. 75, no. 1, 85-98. DOI: 10.3233/CH-190736}}