4.8 Article

Nanolithographic Control of the Spatial Organization of Cellular Adhesion Receptors at the Single-Molecule Level

期刊

NANO LETTERS
卷 11, 期 3, 页码 1306-1312

出版社

AMER CHEMICAL SOC
DOI: 10.1021/nl104378f

关键词

Nanofabrication; nanobiology; mechanobiology; integrin clustering; cell adhesion

资金

  1. National Institutes of Health [R01 GM076415-01 B, PN2EY016586]
  2. National Science Foundation [NSF EF-05-07086]
  3. Nano-scale Science and Engineering Initiative of the National Science Foundation [CHE-0641523]
  4. New York State Office of Science, Technology, and Academic Research (NYSTAR)

向作者/读者索取更多资源

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 four 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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