The Howard P. Isermann Department of Chemical Biological Engineering, and The Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.
Langmuir. 2010 Jun 15;26(12):9695-702. doi: 10.1021/la100363m.
We offer a novel process to render hydrophobic surfaces resistant to relatively small proteins during adsorption. This was accomplished by self-assembly of a well-known natural osmolyte, trimethylamine oxide (TMAO), a small amphiphilic molecule, on a hydrophobic alkanethiol surface. Measurements of lysozyme (LYS) adsorption on several homogeneous substrates formed from functionalized alkanethiol self-assembled monolayers (SAMs) in the presence and absence of TMAO, and direct interaction energy between the protein and functionalized surfaces, demonstrate the protein-resistant properties of a noncovalently adsorbed self-assembled TMAO layer. Molecular dynamics simulations clearly show that TMAO molecules concentrate near the CH(3)-SAM surface and are preferentially excluded from LYS. Interestingly, TMAO molecules adsorb strongly on a hydrophobic CH(3)-SAM surface, but a trade-off between hydrogen bonding with water, and hydrophobic interactions with the underlying substrate results in a nonintuitive orientation of TMAO molecules at the interface. Additionally, hydrophobic interactions, usually responsible for nonspecific adsorption of proteins, are weakly affected by TMAO. In addition to TMAO, other osmolytes (sucrose, taurine, and betaine) and a larger homologue of TMAO (N,N-dimethylheptylamine-N-oxide) were tested for protein resistance and only N,N-dimethylheptylamine-N-oxide exhibited resistance similar to TMAO. The principle of osmolyte exclusion from the protein backbone is responsible for the protein-resistant property of the surface. We speculate that this novel process of surface modification may have wide applications due to its simplicity, low cost, regenerability, and flexibility.
我们提供了一种新颖的方法，使疏水表面在吸附过程中能够抵抗相对较小的蛋白质。这是通过将一种众所周知的天然渗透剂三甲基氧化胺（TMAO），一种小的两亲分子，自组装到疏水烷硫醇表面上来实现的。在有和没有 TMAO 的情况下，对几种由功能化烷硫醇自组装单分子层（SAM）形成的均相基底上的溶菌酶（LYS）吸附的测量，以及蛋白质与功能化表面之间的直接相互作用能，都证明了非共价吸附的自组装 TMAO 层具有抗蛋白质的性质。分子动力学模拟清楚地表明，TMAO 分子在 CH（3）-SAM 表面附近浓缩，并且优先被 LYS 排斥。有趣的是，TMAO 分子在疏水 CH（3）-SAM 表面上强烈吸附，但与水形成氢键和与底层基质发生疏水相互作用之间的权衡，导致 TMAO 分子在界面处的非直觉取向。此外，通常负责蛋白质非特异性吸附的疏水相互作用受 TMAO 的影响较弱。除了 TMAO 之外，还测试了其他渗透剂（蔗糖、牛磺酸和甜菜碱）和 TMAO 的较大同系物（N，N-二甲基庚基胺-N-氧化物）的蛋白质抗性，只有 N，N-二甲基庚基胺-N-氧化物表现出与 TMAO 相似的抗性。渗透剂从蛋白质主链中排除的原理是表面抗蛋白质的原因。我们推测，由于这种表面改性方法的简单性、低成本、可再生性和灵活性，它可能具有广泛的应用。
