Polypeptide Hybrid Particles and Their Constituents

多肽杂化粒子及其成分

• 批准号: 1306262
• 负责人: Paul Russo
• 金额: $ 40.5万
• 依托单位: Louisiana State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1306262&HistoricalAwards=false
• 关键词: Polypeptide; Hybrid; Particles; Their; Constituents

TECHNICAL SUMMARY: The proposed research activities will develop and explore submicron particles having synthetic polypeptide shells atop silica cores, sometimes with magnetic inclusions. The polypeptide shells render the particles responsive to temperature and good sensors of molecular asymmetry, while the silica cores make it possible to direct these functions to a particular location. Whole particles and their individual polypeptide and silica components will be studied. Specifically, the following work will be performed: 1) The effects of core radius, shell polymer coverage, and shell polymer molecular weight on a thermally driven coil-to-helix transition will be assessed by small-angle X-ray and neutron scattering, static and dynamic light scattering, optical rotatory dispersion, and NMR; 2) The particles, acting as very large monomers, will be polymerized into nearly uniform chains by using a magnetic field to align them perpendicular to a striped optical pattern that will initiate a photochemical crosslinking reaction originally developed for proteins; 3) Better understanding of silica core structure, including newly discovered variants, will be achieved by chromatography with fractionation and scattering of X-ray or visible radiation; 4) The stiffness of a water-soluble, uncharged polypeptide will be determined by combined chromatographic and scattering methods; 5) A big difference between the mobility of rigid rods and polypeptide semiflexible filaments will be explored by an optical tracer method; 6) A long-standing problem with the measurement of rigid rod diffusion using pulsed-gradient NMR will be re-assessed using a very high-field-gradient facility.NON-TECHNICAL SUMMARY:Some of nature's most important building blocks and functional engines are made of proteins. Synthetic polypeptides, which can be made in large amounts by simple methods, borrow the protein structure and retain many protein-like features, such as the ability to rotate light and respond to thermal or chemical changes in the environment. The problem is that, even though they are very large molecules, polypeptides are still very small things. This makes them hard to manipulate. The proposed work marries the functionality of bio-inspired polypeptides to the easy manipulation of larger particles using gravitational or magnetic fields. This will be accomplished by placing the polypeptides onto colloidal silica, essentially little balls of glass, resulting in core-shell particles. By adjusting the temperature, the shape of the polypeptide shell will be altered. This will provide information on shape transitions similar to those used by influenza virus to penetrate the human body. Chains of particles crosslinked by the action of light will result in nearly uniform filaments that bring polymer science into the visible regime for easier inspection, while facilitating the creation of even larger structures. Studies on a particularly attractive water-soluble polypeptide will lead to improved understanding of the kinds of polymers used to make high-strength fibers, such as those woven into bullet-proof vests. In terms of societal impact, a middle school chemistry competition will be further expanded in minority-serving districts, thanks to successful attempts to woo professional educators to this cause. New outreach initiatives with a public science & technology middle school will ensue, integrated with real world experience and laboratory research.

技术概要：拟议的研究活动将开发和探索在二氧化硅核上具有合成多肽壳的亚微米颗粒，有时具有磁性包裹体。多肽壳使颗粒对温度和分子不对称性的良好传感器做出响应，而二氧化硅核心使其能够将这些功能引导到特定位置。将研究整个颗粒及其单个多肽和二氧化硅组分。具体来说，将进行以下工作：1）通过小角X射线和中子散射、静态和动态光散射、旋光色散和核磁共振来评估核半径、壳聚合物覆盖度和壳聚合物分子量对热驱动线圈到螺旋转变的影响; 2）颗粒，作为非常大的单体，将通过使用磁场使它们垂直于条纹光学图案排列而聚合成几乎均匀的链为蛋白质开发; 3）将通过具有分级分离和X射线或可见辐射的散射的色谱法来实现对二氧化硅核心结构（包括新发现的变体）的更好理解; 4）将通过组合色谱法和散射方法来确定水溶性、不带电荷的多肽的刚度; 5）用光学示踪法探索刚性杆和多肽半柔性丝的运动性之间的巨大差异; 6）使用脉冲梯度NMR测量刚性棒扩散的一个长期存在的问题将使用非常高的场梯度设备重新评估。非技术性总结：一些自然界最重要的构建模块和功能引擎是由蛋白质组成的。合成多肽可以通过简单的方法大量制造，借用蛋白质结构并保留许多蛋白质样特征，例如旋转光和响应环境中的热或化学变化的能力。问题是，尽管它们是非常大的分子，多肽仍然是非常小的东西。这使得它们很难被操纵。拟议的工作将生物启发多肽的功能与使用重力或磁场轻松操纵较大颗粒结合起来。这将通过将多肽置于胶体二氧化硅（基本上是小玻璃球）上来实现，从而产生核-壳颗粒。通过调节温度，多肽壳的形状将被改变。这将提供类似于流感病毒穿透人体所使用的形状转变的信息。通过光的作用交联的颗粒链将产生几乎均匀的细丝，使聚合物科学进入可见区域，便于检查，同时促进更大结构的创建。对一种特别有吸引力的水溶性多肽的研究将有助于人们更好地理解用于制造高强度纤维的聚合物的种类，例如那些编织成防弹背心的聚合物。在社会影响方面，由于成功地吸引专业教育工作者参与这一事业，中学化学竞赛将在少数民族服务区进一步扩大。与一所公共科学技术中学的新的外联举措将随之而来，与真实的世界经验和实验室研究相结合。