Deng Yang, Wang Yini, Holtz Bryan, Li Jingyi, Traaseth Nathan, Veglia Gianluigi, Stottrup Benjamin J, Elde Robert, Pei Duanqing, Guo Athena, Zhu X-Y
Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Am Chem Soc. 2008 May 14;130(19):6267-71. doi: 10.1021/ja800049f. Epub 2008 Apr 12.
As drug delivery, therapy, and medical imaging are becoming increasingly cell-specific, there is a critical need for high fidelity and high-throughput screening methods for cell surface interactions. Cell membrane-mimicking surfaces, i.e., supported lipid bilayers (SLBs), are currently not sufficiently robust to meet this need. Here we describe a method of forming fluidic and air-stable SLBs through tethered and dispersed cholesterol groups incorporated into the bottom leaflet. Achieving air stability allows us to easily fabricate SLB microarrays from direct robotic spotting of vesicle solutions. We demonstrate their application as cell membrane-mimicking microarrays by reconstituting peripheral as well as integral membrane components that can be recognized by their respective targets. These demonstrations establish the viability of the fluidic and air-stable SLB platform for generating content microarrays in high throughput studies, e.g., the screening of drugs and nanomedicine targeting cell surface receptors.
随着药物递送、治疗和医学成像越来越具有细胞特异性,迫切需要用于细胞表面相互作用的高保真和高通量筛选方法。模拟细胞膜的表面,即支撑脂质双层(SLB),目前还不够坚固,无法满足这一需求。在此,我们描述了一种通过将连接和分散的胆固醇基团掺入底部小叶来形成流体稳定和空气稳定的SLB的方法。实现空气稳定性使我们能够通过直接机器人点样囊泡溶液轻松制备SLB微阵列。我们通过重组可被各自靶点识别的外周膜和整合膜成分,证明了它们作为模拟细胞膜微阵列的应用。这些演示证明了流体稳定和空气稳定的SLB平台在高通量研究中生成内容微阵列的可行性,例如筛选靶向细胞表面受体的药物和纳米药物。