AFM揭示了酸化对LDL和氧化LDL受体相互作用的差异性影响:在动脉生成中的生物力学含义
Kun Wang1,2, Chenhan Sun2, Hongda Zhuang2,3
1School of Life Sciences, Nanchang University, 999 Xuefu Ave., Honggutan District, Nanchang, 330031, Jiangxi, People's Republic of China.
Cellular & molecular biology letters
|March 19, 2025
概括
酸化显著削弱低密度脂蛋白 (LDL) 与其受体 (LDLR) 的结合,但没有氧化LDL (oxLDL) 与食尸受体CD36.6的结合. 这表明在脂蛋白代谢和动脉样硬化中对pH值变化的敏感性不同.
科学领域:
- 生物物理学的生物物理.
- 生物化学 生化学
- 细胞生物学 细胞生物学
背景情况:
- 血脂蛋白与受体的相互作用对新陈代谢和诸如动脉样硬化等疾病至关重要.
- 微环境pH,特别是溶酶体酸化对这些相互作用的影响尚不清楚.
- 研究pH如何影响脂蛋白识别对于了解疾病机制至关重要.
研究的目的:
- 评估原生低密度脂蛋白 (LDL) 和氧化LDL (oxLDL) 与它们各自的受体 (LDL受体 (LDLR) 和CD36) 的pH依赖的识别和相互作用.
- 用原子力显微镜 (AFM) 对活细胞进行这些相互作用的评估.
- 开发和验证一种新的微滴子方法,以提高AFM探头功能和力测量精度.
主要方法:
- 利用原子力显微镜 (AFM) 来测量不同pH值的脂蛋白和受体/细胞之间的结合力.
- 开发了一种基于微滴的新方法,用于AFM探测器功能化,以提高测量精度.
- 将新方法与用于探头功能化的传统沉浸技术进行比较.
主要成果:
- 溶液酸化在pH≤6.4.4时显著降低了LDL-LDLR结合.
- 氧化LDL-CD36结合在pH≤4.4.4之前基本上没有受到影响.
- 微滴AFM方法产生了更准确的相互作用力,揭示了酸化显著降低了LDL-LDLR/细胞相互作用力,但没有oxLDL-CD36/细胞或非特异性相互作用力.
结论:
- LDL-LDLR的识别和相互作用对细胞酸化很敏感.
- 对LDL的氧化修饰在CD36介导的相互作用中赋予了对酸化的耐受性.
- 这些发现为脂蛋白代谢和动脉样硬化病原体提供了新的生物力学见解.
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