Multiscale structure and mechanics of folded protein networks Lorna Dougan , MDH Hughes, Christa Brown, Kalila Cook, Sophie Cussons, David Brockwell, David Head, Najet Mahmoudi University of Leeds, UK Proteins are bionanomachines. These workhorses of the cell are responsible for a vast array of biological functions. Acting in isolation or as part of complex machinery, they perform their function through structural and mechanical changes. Inspired by their specific mechanical properties and diverse functionality, globular folded proteins are versatile nanoscale building blocks for creating responsive biomaterials. However, a major challenge is to construct a theory that connects the mechanical properties of an individual protein and the collective response of a protein network. Here, I will describe our recent efforts to modulate the nanoscale mechanics of single proteins to control their unfolding during protein network formation. We exploit the chemical and mechanical responsiveness of proteins and their photoactivated chemical cross-linking to provide an important route to finely tune the architecture, mechanics, and dynamic relaxation of protein networks. Such predictive control will be advantageous for future smart biomaterials for applications which require responsive and dynamic modulation of mechanical properties and biological function. Towards this goal, I will share our recent efforts to use protein hydrogels for triggered drug delivery and as scaffolds for disease modelling. References 1. MDH Hughes, S Cussons, N Mahmoudi, DJ Brockwell, & L Dougan, L., Tuning Protein Hydrogel Mechanics through Modulation of Nanoscale Unfolding and Entanglement in Postgelation Relaxation , ACS Nano, 2022 2. D Kpelgo, MDG Hughes, L Dougan, M Haddrick, MA Knowles, SD Evans, SA Peyman, Modeling the Mechanical Stiffness of Pancreatic Ductal Adenocarcinoma , Matrix Biology Plus, 2022, 296 3. MDH Hughes, BS Hanson, SE Cussons, N Mahmoudi, DJ Brockwell, L Dougan Control of Nanoscalein situProtein Unfolding Defines Network Architecture and Mechanics of Protein Hydrogels , ACS Nano, 2021, 15, 11296 4. BS Hanson, L Dougan Intermediate Structural Hierarchy in Biological Networks Modulates the Fractal Dimension and Force Distribution of Percolating Clusters , Biomacromolecules, 2021 10, 4191 5. A Aufderhorst-Roberts, MDG Hughes, A Hare, DA Head, N Kapur, DJ Brockwell L Dougan, Reaction Rate Governs the Viscoelasticity and Nanostructure of Folded Protein Hydrogels ,Biomacromolecules,2020, 21:4253
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