DSPE-PEG-PDP调控金表面脂质体破裂行为及tLBM形成机制研究

链接：https://pubs.acs.org/doi/abs/10.1021/la300127m

作者：王曦马修·M·辛德尔王思文雷吉娜·拉根*

摘要：

在水性缓冲液条件下，利用原子力显微镜 (AFM) 研究了脂质体（由大型单层囊泡组成）与基底表面之间的化学亲和力，探究其在金表面驱动囊泡破裂和束缚脂质双层膜 (tLBM) 形成的作用。将 1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-聚乙二醇-2000 -N- [3-(2-吡啶基二硫代)丙酸酯] (DSPE-PEG-PDP) 添加到 1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱 (POPC) 囊泡中，以促进通过金-硫醇盐键形成的相互作用。在有渗透压和无渗透压条件下，AFM 探针探针诱导的导致金表面囊泡破裂的力被量化为 DSPE-PEG-PDP 组分的函数。引起含有 2.5、5 和 10 mol % DSPE-PEG-PDP 的囊泡破裂所需的临界力分别约为 1.1、0.8 和 0.5 nN。对于含有 2.5 mol % DSPE-PEG-PDP 的囊泡，tLBM 形成所需的临界力从 1.1 nN（无渗透压）降至 0.6 nN（5 mM CaCl 2引起的渗透压）。高达 5 nN 的力也不导致纯 POPC 囊泡在金上形成 LBM。DSPE-PEG-PDP 似乎对于在金表面锚定和变形囊泡很重要。这项研究展示了如何利用功能性脂质来调节囊泡-表面相互作用，并阐明了囊泡-底物相互作用在囊泡破裂中的作用。

Abstract

Atomic force microscopy (AFM) studies under aqueous buffer probed the role of chemical affinity between liposomes, consisting of large unilamellar vesicles, and substrate surfaces in driving vesicle rupture and tethered lipid bilayer membrane (tLBM) formation on Au surfaces. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-poly(ethylene glycol)-2000-N-[3-(2-pyridyldithio) propionate] (DSPE-PEG-PDP) was added to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) vesicles to promote interactions via Au–thiolate bond formation. Forces induced by an AFM tip leading to vesicle rupture on Au were quantified as a function of DSPE-PEG-PDP composition with and without osmotic pressure. The critical forces needed to initiate rupture of vesicles with 2.5, 5, and 10 mol % DSPE-PEG-PDP are approximately 1.1, 0.8, and 0.5 nN, respectively. The critical force needed for tLBM formation decreases from 1.1 nN (without osmotic pressure) to 0.6 nN (with an osmotic pressure due to 5 mM of CaCl2) for vesicles having 2.5 mol % DSPE-PEG-PDP. Forces as high as 5 nN did not lead to LBM formation from pure POPC vesicles on Au. DSPE-PEG-PDP appears to be important to anchor and deform vesicles on Au surfaces. This study demonstrates how functional lipids can be used to tune vesicle–surface interactions and elucidates the role of vesicle–substrate interactions in vesicle rupture.

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