Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
J Am Chem Soc. 2022 Jul 13;144(27):12147-12157. doi: 10.1021/jacs.2c02677. Epub 2022 Jun 29.
Mitigation of biofouling and the host's foreign body response (FBR) is a critical challenge with biomedical implants. The surface coating with various anti-fouling materials provides a solution to overcome it, but limited options in clinic and their potential immunogenicity drive the development of more alternative coating materials. Herein, inspired by liquid-liquid phase separation of intrinsically disordered proteins (IDPs) to form separated condensates in physiological conditions, we develop a new type of low-fouling biomaterial based on flexible IDP of FUS protein containing rich hydrophilic residues. A chemical structure-defined FUS IDP sequence tagged with a tetra-cysteine motif (IDP) was engineered and applied for covalent immobilization on various surfaces to form a uniform layer of protein tangles, which boosted strong hydration on surfaces, as revealed by molecular dynamics simulation. The IDP-coated surfaces displayed excellent performance in resisting adsorption of various proteins and adhesion of different cells, platelets, and bacteria. Moreover, the IDP-coated implants largely mitigated the host's FBR compared with bare implants and particularly outperformed PEG-coated implants in reducing collagen encapsulation. Thus, this novel low-fouling and anti-FBR strategy provides a potential surface coating material for biomedical implants, which will also shed light on exploring similar applications of other IDP proteins.
生物污垢和宿主异物反应（FBR）的缓解是生物医学植入物面临的一个关键挑战。通过使用各种抗污材料进行表面涂层是解决这一问题的一种方法，但临床应用的选择有限，且这些材料可能具有免疫原性，这促使人们开发更多替代涂层材料。受无序蛋白（IDP）在生理条件下通过液-液相分离形成分离凝聚物的启发，我们基于富含亲水残基的 FUS 蛋白的柔性 IDP 开发了一种新型低污生物材料。设计并合成了一种带有四半胱氨酸基序（IDP）的化学结构定义的 FUS IDP 序列，并将其用于各种表面的共价固定，以形成均匀的蛋白质缠结层，分子动力学模拟表明这会增强表面的强水合作用。IDP 涂层表面在抵抗各种蛋白质的吸附和不同细胞、血小板和细菌的黏附方面表现出优异的性能。此外，与裸植入物相比，IDP 涂层植入物大大减轻了宿主的 FBR，并且在减少胶原包封方面明显优于 PEG 涂层植入物。因此，这种新型低污和抗 FBR 策略为生物医学植入物提供了一种潜在的表面涂层材料，也为探索其他 IDP 蛋白的类似应用提供了思路。
