title: Force generation by the growth of amyloid aggregates.
abstract: The generation of mechanical forces are central to a wide range of vital biological processes, including the function of the cytoskeleton. Although the forces emerging from the polymerization of native proteins have been studied in detail, the potential for force generation by aberrant protein polymerization has not yet been explored. Here, we show that the growth of amyloid fibrils, archetypical aberrant protein polymers, is capable of unleashing mechanical forces on the piconewton scale for individual filaments. We apply microfluidic techniques to measure the forces released by amyloid growth for two systems: insulin and lysozyme. The level of force measured for amyloid growth in both systems is comparable to that observed for actin and tubulin, systems that have evolved to generate force during their native functions and, unlike amyloid growth, rely on the input of external energy in the form of nucleotide hydrolysis for maximum force generation. Furthermore, we find that the power density released from growing amyloid fibrils is comparable to that of high-performance synthetic polymer actuators. These findings highlight the potential of amyloid structures as active materials and shed light on the criteria for regulation and reversibility that guide molecular evolution of functional polymers.
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom;
authors.forename: Therese W
authors.initials: TW
authors.lastname: Herling
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom;
authors.forename: Gonzalo A
authors.initials: GA
authors.lastname: Garcia
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom;
authors.forename: Thomas C T
authors.initials: TC
authors.lastname: Michaels
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom;
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Grentz
authors.affiliation: Department of Materials Science and Metallurgy, University of Cambridge, Cambridge CB3 0FS, United Kingdom;
authors.forename: James
authors.initials: J
authors.lastname: Dean
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom;
authors.forename: Ulyana
authors.initials: U
authors.lastname: Shimanovich
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom; State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry, East China University of Science and Technology, Shanghai 200237, People's Republic of China;
authors.forename: Hongze
authors.initials: H
authors.lastname: Gang
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom;
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom;
authors.forename: Batuhan
authors.initials: B
authors.lastname: Kav
authors.affiliation: Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, United Kingdom.
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Terentjev
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom; tpjk2@cam.ac.uk cmd44@cam.ac.uk.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom; tpjk2@cam.ac.uk cmd44@cam.ac.uk.
authors.forename: Tuomas P J
authors.initials: TP
authors.lastname: Knowles
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D001696:Biomechanical Phenomena; D002417:Cattle; D044085:Microfluidics; D009113:Muramidase / Q000737:chemistry; D066329:Protein Aggregates
chemical_list: D000682:Amyloid; D066329:Protein Aggregates; D009113:Muramidase
keywords: active materials; amyloidosis; biological force generation; microfluidics; protein misfolding