Nanolithographic control of the spatial organization of cellular adhesion receptors at the single-molecule level.
Nanolithographic control of the spatial organization of cellular adhesion receptors at the single-molecule level.
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DOI：
10.1021/nl104378f
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发表时间：
2011-03-09
期刊：
影响因子：
10.8
通讯作者：
Wind SJ
中科院分区：
文献类型：
--
作者：
Schvartzman M;Palma M;Sable J;Abramson J;Hu X;Sheetz MP;Wind SJ
控制单个分子的位置的能力有望实现广泛的应用，并且是纳米科学和纳米技术的关键挑战。许多生物相互作用尤其对蛋白质的精确几何排列敏感。我们开发了一种将分子级纳米光刻与位点选择性生物化学相结合的技术，以创建单个蛋白质结合位点的仿生阵列。结合位点可以以几乎任何可能的几何形状的异质图案排列，具有几乎无限数量的自由度。我们使用这些阵列来探索细胞外基质 (ECM) 结合配体 RGD (Arg-Gly-Asp) 的几何组织如何影响细胞粘附和扩散。单个整合素结合位点的间距、密度和簇大小的系统变化被用来引发不同的细胞行为。对不同几何排列阵列的细胞铺展测定表明，当至少 4 个配体位点间隔在 60 nm 或更小范围内时，铺展效率显着增加，且不依赖于整体密度。这表明存在以空间和化学计量定义的纤连蛋白的最小基质粘附单元。了解激活特定细胞功能复合物的 ECM 几何结构是控制细胞行为的关键一步。潜在的实际应用范围从新的治疗方法到可以优化愈合而不留疤痕的组织支架的合理设计。更广泛地说，单分子水平的空间控制可以阐明控制单个分子相互作用的因素，并且可以基于分子尺度架构合成新系统。
The ability to control the placement of individual molecules promises to enable a wide range of applications and is a key challenge in nanoscience and nanotechnology. Many biological interactions, in particular, are sensitive to the precise geometric arrangement of proteins. We have developed a technique which combines molecular-scale nanolithography with site-selective biochemistry to create biomimetic arrays of individual protein binding sites. The binding sites can be arranged in heterogeneous patterns of virtually any possible geometry with a nearly unlimited number of degrees of freedom. We have used these arrays to explore how the geometric organization of the extracellular matrix (ECM) binding ligand RGD (Arg-Gly-Asp) affects cell adhesion and spreading. Systematic variation of spacing, density and cluster size of individual integrin binding sites was used to elicit different cell behavior. Cell spreading assays on arrays of different geometric arrangements revealed a dramatic increase in spreading efficiency when at least 4 liganded sites were spaced within 60 nm or less, with no dependence on global density. This points to the existence of a minimal matrix adhesion unit for fibronectin defined in space and stoichiometry. Developing an understanding of the ECM geometries that activate specific cellular functional complexes is a critical step toward controlling cell behavior. Potential practical applications range from new therapeutic treatments to the rational design of tissue scaffolds that can optimize healing without scarring. More broadly, spatial control at the single-molecule level can elucidate factors controlling individual molecular interactions and can enable synthesis of new systems based on molecular-scale architectures.
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