应用计算式蛋白质设计来设计亲属体,以对血管内皮生长因子和血小板衍生生长因子进行亲和控制的输送
Justin E Svendsen1,2,3, Madeleine R Ford1,4, Chandler L Asnes1
1Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, Oregon 97403, United States.
Biomacromolecules
|May 9, 2025
概括
工程蛋白质结合剂 (affibodies) 能够精确控制生物材料中的血管内皮生长因子 (VEGF) 和血小板衍生生长因子 (PDGF) 的释放,增强其生物活性,并使血管生成的新研究成为可能.
科学领域:
- 生物材料科学 生物材料科学
- 蛋白质工程是指蛋白质工程.
- 再生医学是一种再生医学.
背景情况:
- 血管内皮生长因子 (VEGF) 和血小板衍生生长因子 (PDGF) 对血管生成至关重要.
- 现有的生物材料输送系统缺乏对蛋白质释放动力学的精确控制.
- 这种局限性阻碍了对这些生长因子的时间影响的系统研究.
研究的目的:
- 为控制VEGF和PDGF的释放设计蛋白质结合剂 (附属体).
- 为了研究附体介导控制释放对蛋白质生物活性的影响.
- 使用工程生物材料建立一个可调节蛋白质输送平台.
主要方法:
- 酵母表面显示和计算蛋白质设计被用来设计具有不同亲和力的VEGF和PDGF特异性附属体.
- 在基于细胞的测试中,可溶性附属体被测试了它们调节蛋白质生物活性的能力.
- 体结合的水凝被制造出来,在7天的时间内实现可调节的蛋白质释放.
主要成果:
- 成功设计了八个VEGF特异性和八个PDGF特异性附属体.
- 可溶性附属体证明了VEGF诱导的内皮细胞增殖和PDGF响应的发光的调节.
- 附体结合的水凝在7天内提供了可调节的VEGF和PDGF释放.
- 从亲体水凝释放的VEGF和PDGF与对照组相比显示出增强的生物活性.
结论:
- 计算式蛋白质设计可以增强生物材料的功能,以控制蛋白质的输送.
- 工程化附体蛋白相互作用可以延长交付生长因子的生物活性.
- 这种平台可以对高级生物材料应用的蛋白质释放进行精确的时间控制.
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
01:28Role of Hematopoietic Growth Factors
Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
Thrombopoietin (TPO), mainly released by the liver,...
01:07Development of Blood Vessels
The development of the vascular system in a fetus is a complex and intricate process that begins as early as 15 to 16 days post-conception. This process starts outside the embryo, specifically in the mesoderm of the yolk sac, chorion, and connecting stalk. Approximately two days later, the formation of blood vessels occurs within the embryo itself.
The initial formation of this system is facilitated by the small amount of yolk present in the ovum and yolk sac. Blood vessels originate from...
The initial formation of this system is facilitated by the small amount of yolk present in the ovum and yolk sac. Blood vessels originate from...