CELL INTERFACIAL ENGINEERING WITH SOFT LbL SHELLS

主要研究者：Tsukruk，弗拉基米尔建议编号：1402712机构：格鲁吉亚技术研究公司标题：细胞界面工程与软LbL壳生物细胞是复杂的机器，能够做许多事情，仍然超出了工程和科学的能力。这些能力可以通过将细胞保存在保护壳中来使用，然后再将它们带入恶劣的环境中，在那里细胞的功能将被使用。该提案提出了一种新的方式来构建细胞，如酵母和细菌细胞的响应涂层，使用逐层（LbL）技术来制造基于聚合物层，特别是基于丝的聚合物的氢键的聚合物胶囊。这种方法将绕过过去阳离子（带正电荷）LbL聚合物的已知毒性，并解决硅溶胶-凝胶和水凝胶封装技术的一些问题。如果成功开发，该提案中描述的封装方法可能会对保护细胞免受环境影响的新方法产生重大影响，从而使基于细胞的生物传感，基于细胞的治疗和组织工程中的细胞技术成为可能。所提出的方法是系统的，布局良好，涉及制造多层膜的组分的鉴定，研究多层膜的传输特性，然后用选定的聚合物封装酵母和细菌细胞，并研究壳在各种环境中对细胞的保护作用。该提案的新方面包括使用剪切和/或离子强度变化来诱导丝基蛋白质中的构象变化（β-折叠形成）以实现物理交联。计划的方法使用软生物界面，是强大的，半渗透性，和细胞友好的，将有助于研究人员达到他们的最终目标，获得界面组织，运输性能的理解，以及壳和细胞表面之间的相互作用机制，这是必要的，以保持基因工程微生物细胞的活力和功能。

PI: Tsukruk, Vladimir Proposal Number: 1402712 Institution: Georgia Tech Research Corp Title: CELL INTERFACIAL ENGINEERING WITH SOFT LbL SHELLSBiological cells are complex machineries that are able to do many things that are still beyond the capabilities of engineering and science. Those capabilities can be used by preserving the cells in a protective shell before bringing them into a hostile environment, where the cell's functionalities are to be used. This proposal presents a new way to construct responsive coatings for cells, such as yeast and bacterial cells, using layer-by-layer (LbL) techniques to make polymeric capsules based on hydrogen bonding of the polymeric layers, particularly silk-based polymers. This proposed approach will bypass the known toxicity of past cationic (positively charged) LbL polymers, as well as resolve some of the issues with silica sol-gel and hydrogel encapsulation technologies. The encapsulation methodology described in this proposal, if successfully developed, could lead to a high impact on new ways to protect cells from their environments and thus enable cellular technologies in cell-based biosensing, cell-based therapies, and tissue engineering.The proposed approach is systematic and well laid out, involving identification of components from which to fabricate the multilayers, studies of the transport properties of the multilayers, and then encapsulation of yeast and bacterial cells with the select polymers and investigation of protective effects of the shells on the cells as they are challenged in various environments. Novel aspects of the proposal include the use of shear and/or ionic strength changes into induce conformational changes (beta-sheet formation) in silk-based proteins to achieve physical cross-linking. The planned approach of using soft bio-interfaces that are robust, semipermeable, and cyto-friendly will help the investigators to reach their ultimate goal of gaining an understanding of interfacial organization, transport properties, and the mechanism of interactions between the shells and cell surfaces that are necessary to preserve the viability and function of genetically engineered microbial cells.