Department of Mechanical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK.
Ann Biomed Eng. 2020 Jan;48(1):357-366. doi: 10.1007/s10439-019-02353-7. Epub 2019 Sep 13.
The lipid membrane of endothelial cells plays a pivotal role in maintaining normal circulatory system functions. To investigate the response of the endothelial cell membrane to changes in vascular conditions, an atomistic model of the lipid membrane interspersed with Syndecan-4 core protein was established based on experimental observations and a series of molecular dynamics simulations were undertaken. The results show that flow results in continuous deformation of the lipid membrane, and the degree of membrane deformation is not in monotonic relationship with the environmental changes (either the changes in blood velocity or the alteration of the core protein configuration). An explanation for such non-monotonic relationship is provided, which agrees with previous experimental results. The elevation of the lipid membrane surface around the core protein of the endothelial glycocalyx was also observed, which can be mainly attributed to the Coulombic interactions between the biomolecules therein. The present study demonstrates that the blood flow can deform the lipid membrane directly via the interactions between water molecules and lipid membrane atoms thereby affecting mechanosensing; it also presents an additional force transmission pathway from the flow to the lipid membrane via the glycocalyx core protein, which complements previous mechanotransduction hypothesis.
内皮细胞的脂膜在维持正常循环系统功能方面起着关键作用。为了研究血管条件变化对内皮细胞膜的响应,基于实验观察建立了嵌入 Syndecan-4 核心蛋白的脂膜的原子模型,并进行了一系列分子动力学模拟。结果表明,流动导致脂膜的连续变形,膜变形的程度与环境变化(无论是血流速度的变化还是核心蛋白构象的改变)并非呈单调关系。对此非单调关系提供了一种解释,与之前的实验结果一致。还观察到内皮细胞糖萼核心蛋白周围的脂膜表面升高,这主要归因于其中生物分子之间的库仑相互作用。本研究表明,血流可以通过水分子和脂膜原子之间的相互作用直接使脂膜变形,从而影响机械敏感性;它还通过糖萼核心蛋白提供了从流动到脂膜的另一种力传递途径,补充了之前的力学转导假说。