MESONET: Exploiting in situ protein unfolding to understand and control mesoscopic network formation

MESONET：利用原位蛋白质展开来理解和控制介观网络形成

• 批准号: EP/X023524/1
• 负责人: Lorna Dougan
• 金额: $ 227.98万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX023524%2F1
• 关键词: MESONET; Exploiting; situ; protein; unfolding

A major challenge in soft matter and biological physics is to construct a theory that connects the mechanical properties of an individual biopolymer and the collective response of a network of such biopolymers. While huge advancements have been made in the characterisation of biopolymers and their networks at the nanoscale and macroscale, the physics which describes the translation of mechanical properties across scales remains elusive. The key to unlocking this complexity is the use of Nature's bionanomachines-proteins as model systems, which possess evolutionary evolved stability and function, and which can be exploited to achieve in situ control of mesoscale network formation. My vision is to uncover the rich complexity of mesoscale protein network formation. I will achieve this through the development of a powerful suite of experimental and modelling tools which provide unprecedented access to force propagation and mesoscale network formation. A key strength of my approach is that the role of nanoscale changes and modifications in network architecture can be decoupled, so that they can be individually controlled to influence the network properties. I will develop rapid frame rate acquisition of in situ network formation to reveal how nanoscale mechanics and relaxation regulates mesoscale network formation. I will design and engineer mechanophores to measure force propagation and network relaxation at multiple length-and time-scales. I will exploit controlled mechanical deformation within the heterogeneous protein networks to yield novel technological advancements in designer soft matter for controlled small molecule diffusion and triggered release. This frontier science will deliver novel experimental and modelling tools for the soft matter community, uncover the fundamental physics which describes the translation of mechanics across scales and provide a paradigm shift in the design of soft matter materials for future applications.

软物质和生物物理学的一个主要挑战是构建一个理论，将单个生物聚合物的机械特性与这种生物聚合物网络的集体响应联系起来。虽然在纳米尺度和宏观尺度上对生物聚合物及其网络的表征已经取得了巨大的进步，但描述机械性能跨尺度转换的物理学仍然难以捉摸。解开这一复杂性的关键是使用自然界的生物机器蛋白质作为模型系统，它具有进化的稳定性和功能，并可以被利用来实现原位控制中尺度网络的形成。我的愿景是揭示中尺度蛋白质网络形成的丰富复杂性。我将通过开发一套强大的实验和建模工具来实现这一目标，这些工具提供了前所未有的力量传播和中尺度网络形成的途径。我的方法的一个关键优势是，纳米级变化和修改在网络架构中的作用可以解耦，因此它们可以单独控制以影响网络属性。我将开发快速帧速率采集原位网络形成，以揭示纳米力学和松弛如何调节中尺度网络形成。我将设计和工程机械测量力传播和网络松弛在多个长度和时间尺度。我将利用异质蛋白质网络内的受控机械变形，在设计软物质方面取得新的技术进步，以实现受控小分子扩散和触发释放。这一前沿科学将为软物质社区提供新颖的实验和建模工具，揭示描述力学跨尺度转换的基础物理学，并为未来应用的软物质材料设计提供范式转变。

项目成果

Diversity of viscoelastic properties of an engineered muscle-inspired protein hydrogel.

工程肌肉启发的蛋白质水凝胶的粘弹性特性的多样性。

• DOI: 10.1039/d2sm01225a
• 发表时间: 2023
• 期刊: Soft matter
• 影响因子: 3.4
• 作者: Aufderhorst-Roberts A

Modeling the mechanical stiffness of pancreatic ductal adenocarcinoma.

• DOI: 10.1016/j.mbplus.2022.100109
• 发表时间: 2022-06
• 期刊: Matrix biology plus
• 作者: Kpeglo D;Hughes MDG;Dougan L;Haddrick M;Knowles MA;Evans SD;Peyman SA
• 通讯作者: Peyman SA

Structural and mechanical properties of folded protein hydrogels with embedded microbubbles.

• DOI: 10.1039/d2bm01918c
• 发表时间: 2023-04-11
• 期刊: Biomaterials science
• 影响因子: 6.6
• 作者: Brown CP;Hughes MDG;Mahmoudi N;Brockwell DJ;Coletta PL;Peyman S;Evans SD;Dougan L
• 通讯作者: Dougan L

Tuning Protein Hydrogel Mechanics through Modulation of Nanoscale Unfolding and Entanglement in Postgelation Relaxation.

• DOI: 10.1021/acsnano.2c02369
• 发表时间: 2022-07-26
• 期刊: ACS NANO
• 影响因子: 17.1
• 作者: Hughes, Matt D. G.;Cussons, Sophie;Mahmoudi, Najet;Brockwell, David J.;Dougan, Lorna
• 通讯作者: Dougan, Lorna