Abstract：
Elastin-like polypeptides (ELPs) are a promising material platform for engineering stimuli-responsive biomaterials, as ELPs undergo phase separation above a tunable transition temperature. ELPs with phase behavior that is isothermally regulated by biological stimuli remain attractive for applications in biological systems. Herein, we report protease-driven phase separation of ELPs. Protease-responsive \"cleavable\" ELPs comprise a hydrophobic ELP block connected to a hydrophilic ELP block by a protease cleavage site linker. The hydrophilic ELP block acts as a solubility tag for the hydrophobic ELP block, creating a temperature window in which the cleavable ELP reactant is soluble and the proteolytically generated hydrophobic ELP block is insoluble. Within this temperature window, isothermal, protease-driven phase separation occurs when a critical concentration of hydrophobic cleavage product accumulates. Furthermore, protease-driven phase separation is generalizable to four compatible protease-cleavable ELP pairings. This work presents exciting opportunities to regulate ELP phase behavior in biological systems using proteases.
摘要：
弹性蛋白样多肽（ELPs）是一个有前途的材料平台工程刺激响应性生物材料，当ELPs在可调转变温度以上经历相分离时。具有由生物刺激等温调节的相行为的ELP对于在生物系统中的应用仍然具有吸引力。在这里，我们报道了蛋白酶驱动的ELPs相分离。蛋白酶响应性“可裂解”ELP包含通过蛋白酶裂解位点接头连接至亲水性ELP嵌段的疏水性ELP嵌段。亲水性ELP嵌段充当疏水性ELP嵌段的溶解度标签，产生温度窗口,其中可裂解的ELP反应物是可溶的并且蛋白水解产生的疏水性ELP嵌段是不可溶的。在这个温度窗口内,等温,当临界浓度的疏水裂解产物积累时,发生蛋白酶驱动的相分离。此外，蛋白酶驱动的相分离可推广到四个相容的蛋白酶可裂解的ELP配对。这项工作为使用蛋白酶在生物系统中调节ELP相行为提供了令人兴奋的机会。
