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首页> 外文学位 >Structural transitions in self-assembled lipid systems driven by induced curvature: From cell-penetrating peptides to programmable vesicles .
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Structural transitions in self-assembled lipid systems driven by induced curvature: From cell-penetrating peptides to programmable vesicles .

机译：由诱导曲率驱动的自组装脂质系统的结构转变：从细胞穿透肽到可编程囊泡。

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摘要

Arginine rich cell-penetrating peptides are short cationic peptides capable of traversing the plasma membranes of eukaryotic cells. While successful intracellular delivery of many biologically active macromolecules has been accomplished using these peptides, their mechanisms of cell entry are still under investigation. Ionic interactions between the highly cationic peptides and the anionic cell membrane and other anionic molecules on the cell surface are believed to be the initial step in the internalization process.;We examined the interactions of TAT peptide with prototypical cell membranes using confocal microscopy and synchrotron small angle x-ray scattering (SAXS) and studied the effect of membrane charge and intrinsic curvature. We find that the TAT peptide induces negative Gaussian ('saddle-splay') membrane curvature, which is topologically required for pore formation. TAT peptide drastically remodels vesicles into a porous 'sponge-like' bicontinuous manifold. By applying ideas from coordination chemistry, soft condensed matter physics and differential geometry, we propose a geometric mechanism facilitated by both electrostatics and bidentate hydrogen bonding.;We also examined the interactions of other arginine rich cell-penetrating peptides, including Antp and oligoarginine, with model cell membranes, and find that the transduction activity correlates with induction of negative Gaussian curvature. The negative Gaussian membrane curvature is broadly enabling and its induction can lower the free energy barriers for a range of different entry mechanisms, such as direct translocation as well as endocytotic pathways. Furthermore, we show that the TAT peptide interacts strongly with actin cytoskeleton, which enhances membrane deformation and cytoskeleton reorganization necessary for endocytotic processes. We propose a mechanism that explains how a relatively simple molecule, like the TAT peptide, facilitates direct entry and multiple endocytotic mechanisms.
机译：富含精氨酸的细胞穿透肽是能够穿越真核细胞质膜的短阳离子肽。尽管使用这些肽已经成功地完成了许多具有生物活性的大分子的细胞内递送，但是它们的细胞进入机制仍在研究中。高阳离子肽与阴离子细胞膜和细胞表面其他阴离子分子之间的离子相互作用被认为是内在化过程的第一步。;我们使用共聚焦显微镜和同步加速器对TAT肽与原型细胞膜的相互作用进行了研究。角x射线散射（SAXS）并研究了膜电荷和固有曲率的影响。我们发现，TAT肽诱导负高斯（“马鞍形”）膜曲率，这是孔形成的拓扑结构所必需的。 TAT肽可将囊泡彻底重塑成多孔的“海绵状”双连续歧管。通过应用配位化学，软凝聚态物理和微分几何学的思想，我们提出了一种通过静电和双齿氢键促进的几何机理。我们还研究了其他富含精氨酸的细胞穿透肽（包括Antp和低聚精氨酸）与模拟细胞膜，发现其转导活性与负高斯曲率的诱导相关。负高斯膜曲率在很大程度上是可以实现的，其感应可以降低自由能垒对一系列不同进入机制的影响，例如直接易位以及胞吞途径。此外，我们表明，TAT肽与肌动蛋白细胞骨架强烈相互作用，从而增强了膜变形和内吞过程所需的细胞骨架重组。我们提出一种机制来解释相对简单的分子（如TAT肽）如何促进直接进入和多种内吞机制。

著录项

  • 作者

    Mishra, Abhijit.;

  • 作者单位

    University of Illinois at Urbana-Champaign.;

  • 授予单位 University of Illinois at Urbana-Champaign.;
  • 学科 Biophysics General.;Engineering Materials Science.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 144 p.
  • 总页数 144
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-17 11:36:56

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