Fusion of biomimetic stealth probes into lipid bilayer cores
Fusion of biomimetic stealth probes into lipid bilayer cores
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DOI：
10.1073/pnas.0909250107
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发表时间：
2010-03-30
影响因子：
11.1
通讯作者：
Melosh, Nicholas A.
中科院分区：
文献类型：
--
作者：
Almquist, Benjamin D.;Melosh, Nicholas A.
许多生物材料被设计用于调节人工和天然表面之间的相互作用。然而，当材料通过细胞膜本身插入时，膜的内边缘和材料表面之间形成的界面没有很好地理解和控制。在这里，我们证明，通过复制纳米级的跨膜蛋白的疏水-疏水-亲水结构，人工“隐形”探针自发插入和锚内的脂质双层核心，形成一个高强度的接口。这些纳米级的疏水带很容易制造的金属探针，通过功能化的暴露的侧壁，而不是通过光刻蒸发的Au金属层。使用原子力显微镜（AFM）上的厚叠层的脂质双层，以消除基板的影响，直接测量的渗透力和粘附力的正丁烷乙烷和十二烷乙烷官能化的探针。疏水性探针与亲水性探针的渗透动力学完全不同。5-和10 nm厚的疏水功能化的探针天然地驻留在脂质核心内，而亲水性探针保留在水性区域中。令人惊讶的是，用短的丁炔乙烷链对探针渗透的障碍（E-o;5（nm）= 21.8k（B）T，E-o;10（nm）= 15.3k（B）T）显著高于较长的十二烷基硫醇链（E-o;5（nm）= 14.0k（B）T，E-o; 10 nm = 10.9 k（B）T），表明除了疏水性之外，分子迁移率和取向在确定界面稳定性方面也起作用。这些结果突出了一个新的策略，设计人工细胞界面，可以无损地穿透脂质双层。
Many biomaterials are designed to regulate the interactions between artificial and natural surfaces. However, when materials are inserted through the cell membrane itself the interface formed between the interior edge of the membrane and the material surface is not well understood and poorly controlled. Here we demonstrate that by replicating the nanometer-scale hydrophilic-hydrophobic-hydrophilic architecture of transmembrane proteins, artificial "stealth" probes spontaneously insert and anchor within the lipid bilayer core, forming a high-strength interface. These nanometer-scale hydrophobic bands are readily fabricated on metallic probes by functionalizing the exposed sidewall of an ultrathin evaporated Au metal layer rather than by lithography. Penetration and adhesion forces for butanethiol and dodecanethiol functionalized probes were directly measured using atomic force microscopy (AFM) on thick stacks of lipid bilayers to eliminate substrate effects. The penetration dynamics were starkly different for hydrophobic versus hydrophilic probes. Both 5- and 10 nm thick hydrophobically functionalized probes naturally resided within the lipid core, while hydrophilic probes remained in the aqueous region. Surprisingly, the barrier to probe penetration with short butanethiol chains (E-o;5 (nm) = 21.8k(b)T, E-o;10 (nm) = 15.3k(b)T) was dramatically higher than longer dodecanethiol chains (E-o;5 (nm) = 14.0k(b)T, E-o;10 nm = 10.9k(b)T), indicating that molecular mobility and orientation also play a role in addition to hydrophobicity in determining interface stability. These results highlight a new strategy for designing artificial cell interfaces that can nondestructively penetrate the lipid bilayer.