Dynamic Interactions between Lipid-Tethered DNA and Phospholipid Membranes.
Dynamic Interactions between Lipid-Tethered DNA and Phospholipid Membranes.
复制标题
DOI：
10.1021/acs.langmuir.8b02271
复制
发表时间：
2018-12-11
期刊：
影响因子：
--
通讯作者：
Howorka S
中科院分区：
文献类型：
--
作者：
Arnott PM;Joshi H;Aksimentiev A;Howorka S
在DNA纳米技术、合成生物学和细胞生物学研究中，脂质锚定的DNA可以将功能性货物附着到双层膜上。为了优化DNA锚定，需要了解DNA-膜相互作用的结合强度，程度和结构动力学。在这里，我们使用实验和分子动力学（MD）模拟，以确定如何膜结合胆固醇修饰的DNA依赖于静电和立体因素，涉及脂质头基电荷，双链或单链DNA，和缓冲液的组成。这些实验区分了游离和膜囊泡结合的DNA，从而揭示了锚定DNA的表面密度及其结合亲和力，这是以前不知道的。Kd值在8.5 ± 4.9至466 ± 134 μ M的范围内，其中带负电荷的头部基团由于与带负电荷的DNA的静电排斥而导致弱结合。原子分子动力学模拟解释了这一发现，并阐明了锚定DNA的动态性质，如蘑菇状构象的单链DNA盘旋在双层表面上，而不是一个直线上升的构象的双链DNA。对膜的结合强度以及DNA与分子货物杂交的分子可及性的生物物理学见解预计将有助于创建用于研究和纳米生物技术的天然膜纳米孔和细胞骨架的仿生DNA版本。
Lipid-anchored DNA can attach functional cargo to bilayer membranes in DNA nanotechnology, synthetic biology, and cell biology research. To optimize DNA anchoring, an understanding of DNA-membrane interaction in terms of binding strength, extent, and structural dynamics is required. Here we use experiments and molecular dynamics (MD) simulations to determine how membrane binding of cholesterol-modified DNA depends on electrostatic and steric factors involving lipid head-group charge, duplexed or single stranded DNA, and buffer composition. The experiments distinguish between free and membrane vesicle-bound DNA, and thereby reveal the surface density of anchored DNA and its binding affinity, something which had previously not been known. The Kd values range from 8.5 ± 4.9 to 466 ± 134 uM whereby negatively charged head-groups led to weak binding due to the electrostatic repulsion to the negatively charged DNA. Atomistic molecular dynamics simulations explain the findings and elucidate the dynamic nature of anchored DNA such as the mushroom-like conformation of single stranded DNA hovering over the bilayer surface in contrast to a straight-up conformation of double stranded DNA. The biophysical insight into binding strength to membranes as well as the molecular accessibility of DNA for hybridization to molecular cargo is expected to facilitate creating biomimetic DNA versions of natural membrane nanopores and cytoskeletons for research and nanobiotechnology.
登录
查看更多内容
影响因子：
10.8
作者：
Dutta PK;Zhang Y;Blanchard AT;Ge C;Rushdi M;Weiss K;Zhu C;Ke Y;Salaita K
通讯作者：
Salaita K
影响因子：
3.3
作者：
Gambinossi, Filippo;Banchelli, Martina;Baglioni, Piero
通讯作者：
Baglioni, Piero
影响因子：
38.3
作者：
Burns, Jonathan R.;Seifert, Astrid;Howorka, Stefan
通讯作者：
Howorka, Stefan
影响因子：
5.5
作者：
Hart, Katarina;Foloppe, Nicolas;Baker, Christopher M.;Denning, Elizabeth J.;Nilsson, Lennart;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
影响因子：
17.1
作者：
Gopfrich, Kerstin;Li, Chen-Yu;Ricci, Maria;Bhamidimarri, Satya Prathyusha;Yoo, Jejoong;Gyenes, Bertalan;Ohmann, Alexander;Winterhalter, Mathias;Aksimentiev, Aleksei;Keyser, Ulrich F.
通讯作者：
Keyser, Ulrich F.