在响应生理学相关的pH波动时,对原蛋白水凝结构和特性进行多模式的表征
Orit Bronner-Shtrauchler1, Einat Nativ-Roth2, Daniel Sevilla Sanchez2
1Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Acta biomaterialia
|February 28, 2024
概括
细胞外基质 (ECM) pH 的变化改变了原蛋白的结构和特性. 酸性条件会导致方向失调和机械强度降低,但中性pH值会恢复原生原蛋白的特性.
科学领域:
- 生物材料科学 生物材料科学
- 生物物理学的生物物理.
- 细胞生物学 细胞生物学
背景情况:
- 细胞外基质 (ECM) 主要由原组成,对组织结构和功能至关重要.
- 病理状况,如固体瘤和慢性伤口,在ECM内涉及显著的pH波动.
- 之前的研究集中在原形成 (纤维形成) 期间的pH影响上,而不是预先形成的原结构.
研究的目的:
- 研究pH值波动对预制原体水凝结构,特性和功能的影响.
- 了解微环境pH值的变化如何影响水合原体,模仿生理ECM.
- 在疾病相关的pH条件下分析原干扰.
主要方法:
- 使用I型原蛋白水凝来模拟生理ECM.
- 使用冷扫描电子显微镜 (cryo-SEM) 进行水合原蛋白的高分辨率成像.
- 应用人工智能辅助图像分析以量化结构变化.
- 测量质性质,包括储存模量和透性.
主要成果:
- 尽管存在相关的pH值变化,但原蛋白的二次结构仍然稳定.
- 与生理pH相比,将pH值降低到6.5会导致原纤维较短,稀少,且失方向.
- 原蛋白水凝在pH 7和7.8时表现出较高的储存模量和较低的透率,而不是pH 6.5和7.4.
- 将酸性原蛋白恢复到中性的pH值恢复了它的原生结构和粘弹性特性.
结论:
- 微环境的pH波动显著改变了原纤维的形态和机械特性.
- 这些由pH诱导的原结构变化可以是可逆的.
- 了解这些依赖pH值的原蛋白变化为涉及ECM变化的疾病提供了潜在的治疗策略.
相关概念视频
What are Proteins?
Overview
Water: A Bronsted-Lowry Acid and Base
The reaction between a Brønsted-Lowry acid and water is called acid ionization. For example, when hydrogen fluoride dissolves in water and ionizes, protons are transferred from hydrogen fluoride molecules to water molecules, yielding hydronium ions and fluoride ions:
pH Scale
Hydronium and hydroxide ions are present both in pure water and in all aqueous solutions, and their concentrations are inversely proportional as determined by the ion product of water (Kw). The concentrations of these ions in a solution are often critical determinants of the solution’s properties and the chemical behaviors of its other solutes. Two different solutions can differ in their hydronium or hydroxide ion concentrations by a million, billion, or even trillion times. A common means of...
pH
The potential of hydrogen (pH) is a measure of the acidity or basicity of a water-based solution determined by the concentration of hydronium ions (H3O+). In one liter of pure water at neutral pH, there are 1×10−7 moles of hydronium ions. However, the extensive range of hydronium ion concentrations present in water-based solutions makes measuring pH in moles cumbersome. Therefore, a pH scale was developed to convert moles of hydronium ions into the negative logarithm of the hydronium ion...
What are Proteins?
Proteins are polymers of amino acids linked together by peptide bonds. Proteins and polypeptides are interchangeably used to refer to long chains of amino acids. However, polypeptides have a molecular weight of fewer than 10,000 daltons, while proteins have greater molecular weight. Polypeptides with less than 20 amino acids are called oligopeptides or simply peptides. Interactions among the constituent amino acid side chains of proteins help them fold into a stable 3-dimensional structure...
Extraction: Effects of pH
Consider a neutral form of an amine, B, with a partition coefficient, K, in a liquid mixture containing organic and aqueous phases. The pH of the aqueous phase affects the charge on acidic and basic solutes, and the charged form is usually more soluble in the aqueous phase. Suppose the conjugate acid form of the amine is soluble only in the aqueous phase while the base form is soluble in both phases. Then the distribution coefficient, D, can be given as the ratio of amine concentration in the...


