以分子動力模擬探討單股與雙股去氧核醣核酸吸附於微懸臂梁生物感測器之表面應力

Abstract

微懸臂梁生物感測器具有高靈敏度、不須特殊標的物(label free)、 即時性、成本低廉等優點，目前已廣泛用在生物辨識感測的研究上， 但其中生物分子感測造成微懸臂梁撓曲的機制尚不明確，而要探討這 些微觀尺度的現象，利用分子尺度模擬為一可行的方式。DNA 雜交 (DNA hybridization)現象不管在實驗或模擬皆有文獻探討雜交的機制， 其中少部分模擬基板表面上的DNA 雜交現象(Wong et al., 2001; Wong et al., 2004a; Wong et al., 2004b; Jayaraman et al., 2006; Jayaraman et al., 2007; Monti et al., 2010)，但焦點皆在DNA 雜交的過程，很少將雜交現 象與微懸臂梁感測器表面結合探討其對表面應力的影響。本研究利用 模擬單股與雙股DNA 吸附於金表面的方式來討論DNA 雜交前與雜交 後對金表面應力的影響。 本論文先就微懸臂梁生物感測器做一簡介，並回顧近年DNA 雜 交實驗與模擬的現況，再介紹研究中使用的分子動力方法、表面應力 計算法、模型與使用的原子勢能。模擬中利用兩種不同的模型，第一 種包含金原子與DNA 模擬DNA 吸附後造成的表面應力來源，結果顯 示DNA 造成的貢獻較金原子表面的貢獻小一個數量級，且環境中離子 與水的效應會影響微懸臂梁的上彎或下彎，第二種模型利用固定DNA 尾端原子的方式控制DNA 間的距離來模擬DNA 間的交互作用與覆蓋 率對表面應力的影響，當覆蓋率越高，單股與雙股DNA 應力差值的壓 應力也越高，表面應力的主要來源為DNA 間的電量排斥、離子間的斥 力與DNA 與離子的吸引力，模擬的結果與實驗觀察的現象吻合。最後 再對此主題的研究提出建議與未來方向的參考。

Micro-cantilever biosensors are one of the rapidly developing biosensors with numerous advantages like high sensitivity, wide applicability and low cost. It can detect various specific bio-recognitions by the surface stress induced bending of bio-molecular adsorption. Despite its wide applications, the mechanism of how bio-molecular adsorption influences the surface stress is still not clear. The aim of this study is to simulate single-stranded and double-stranded DNA adsorbing on micro-cantilever surface and investigate the surface stress origin of micro-cantilever bending observed from DNA hybridization experiments. We used classical molecular dynamics simulation and two different models to study surface stress of DNAs on the surface. The first model contained Au surfaces and DNAs in the water environment with ions. Because of the asymmetric of DNA conformations after adsorption on the top and bottom surfaces, two different bending behaviors were obtained from the simulation results. We found that tensile surface stress resulted mainly from interactions of environment with Au/DNA. The second model solely contained anchored DNAs in the water environment with ions and used to investigate the relationship between DNA coverage and surface stress. We found that the compressive surface increased when the coverage increased. The tensile surface stress from contributions of ions indicated the influence of higher ionic concentrations on bending behavior. These simulation results provide guidance for future design of experiments.