CAREER: Bottlebrush polymers as gateways to multiresponsive structures

活细胞通过由跨膜蛋白组成的膜孔来控制进入细胞的物质和离开细胞的物质，这些膜孔起着守门人的作用。通过这样做，细胞能够评估环境中发生的事情并做出相应的反应。受此功能的启发，本CAREER项目的目标是开发独特的策略，将响应性孔隙形成结构引入聚合物囊泡中。具体来说，这项工作旨在使用管状大分子，被称为核壳瓶刷，来模拟跨膜蛋白的门控功能，并使一类新的材料能够对机械激活、光学刺激、酸度变化等做出反应。这些细胞状结构将有助于设计多响应系统，最终可能能够模仿触觉、视觉和嗅觉等感官。在这项研究成果的基础上，人们可以很容易地设想将类似的系统用于诸如靶向药物输送，传感以及高价值应用的主动过滤装置等应用。在这些学术活动的同时，社区活动将被用来向公众，特别是少数族裔推广STEM教育。这些活动将包括超越艺术和科学的倡议，鼓励崭露头角的小学科学家成为创造者，并为研究生提供成为未来科学/技术全球思想家和领导者的工具。本研究的潜在目标是理解指导块状线性和瓶刷（BB）两亲共聚物共组装的关键现象，以制造生物启发的多响应聚合物体。为此，我们设计了一个综合的定向策略，该策略依赖于三个相互关联的目标：(i)两亲性三嵌段共聚物的结构评估（例如刚度、交叉、侧链长度），（ii）了解两亲性线性和BB嵌段共聚物的共组装，以及（iii）通过使用pH、光和机械力等刺激将形成孔的BB三嵌段结合到膜中，从而赋予聚合体多刺激响应性。可以在BBs中控制的众多参数（通常是正交的），例如持久性长度、嫁接长度和密度，使它们对这个项目特别有吸引力。这项工作的目的是带来迄今为止尚未开发的复杂聚合物结构的自组装及其与传统线性嵌段共聚物的共组装方面。这项工作的更广泛的结果可能在制造复杂的、模拟细胞过程的区隔聚合体中实现，但也可以在诸如活性过滤膜和/或依赖于按需货物释放的靶向递送系统中实现。该计划亦会推行多项活动，以鼓励多元化和推广STEM，并加强少数族裔的参与。这些活动将包括创客会议和黑客马拉松，以及通过利用刺激响应材料固有的视觉吸引力来融合艺术和科学。促进全球科学观点和在课程中纳入主动学习是该CAREER项目的其他综合目标之一。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

Part 1: Non-technical summaryLiving cells control what enters them and what leaves using carefully regulated transport across membrane pores made up of transmembrane proteins, which act as gatekeepers. In doing so, cells are able to assess what goes on in their environment and respond accordingly. Inspired by this function, the objective of this CAREER project is to develop unique strategies that enable the introduction of responsive pore-forming structures into polymeric vesicles. Specifically, the work aims to use tube-like macromolecules, known as core-shell bottlebrushes, to emulate the gating function of transmembrane proteins and enable a new class of materials that respond to mechanical activation, optical stimulation, changes in acidity, etc. These cell-like structures will help devise multiresponsive systems that may ultimately be capable of mimicking senses such as touch, sight, and smell. Building upon the results of this research endeavor, one can readily envision to use similar systems for applications such as targeted drug delivery, sensing, as well as active filtration devices for high-value applications. Concomitantly with these scholarly activities, community events will be used to promote STEM education to the general public and, particularly, underrepresented minorities. These activities will include initiatives that transcend the arts and sciences, encourage budding grade-school scientists to become makers, and provide graduate students with the tools to be scientific/technological global thinkers and leaders of tomorrow.Part 2: Technical summaryThe underlying goal of this research is to comprehend the crucial phenomena directing the co-assembly of blocky linear and bottlebrush (BB) amphiphilic copolymers towards the fabrication of bioinspired multiresponsive polymersomes. To this end, an integrative and directed strategy that relies on three connected aims was devised: (i) structural evaluation of amphiphilic triblock copolymers (e.g. stiffness, interdigitation, side-chain length), (ii) understanding of the co-assembly of amphiphilic linear and BB block copolymers, and (iii) bestowing of multi-stimuli-responsiveness to polymersomes by incorporating pore-forming BB triblocks in membranes using stimuli such as pH, light, and mechanical force. The numerous parameters that can be controlled in BBs, often orthogonally, such as persistence length, grafting length and density, make them especially alluring for this project. This work aims to bring about hitherto underexplored aspects of the self-assembly of complex polymeric architectures and their co-assembly with conventional linear block copolymers. The broader results of this work may be implemented in the fabrication of intricate, compartmentalized polymersomes that emulate cellular processes, but also in systems such active filtration membranes and/or targeted delivery systems that rely on on-demand cargo release. The PI will also implement several activities to encourage diversity and promote STEM universally and enhance participation of underrepresented minorities. These activities will include maker conferences and hackathons, as well as blending arts and sciences by exploiting the inherent visual appeal of stimuli-responsive materials. Promotions of global views of sciences and inclusion of active learning in curricula are amongst the other integrated objectives of this CAREER project..This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.