Contributed Talk - Friday, 17 September I 14:25 PM (CEST)
Prof. F. Simone Ruggeri: "Single-Molecule AFM and Infrared Nanospectroscopy for Bioscience"
Wageningen University, Netherlands
Biological processes at the base of life and disease rely on a wide class of protein-based biomolecular machines that have characteristic nanoscale physical dimensions and whose function emerges from a correlation between their chemical and structural properties. A fundamental objective of modern methods in physics, chemistry and biology is the comprehension of how the physical-chemical state and heterogeneity of biomolecules determine their role in cellular function and disease. Here, we first demonstrate that high-resolution Atomic Force Microscopy (AFM) and single-molecule statistical analysis are capable to unravel the complex and heterogeneous process of protein misfolding and aggregation into amyloid fibrils in order to shed light onto the molecular basis of cell malfunction in neurodegenerative disorders.[1-3] Then, to overcome the limitations of conventional imaging microscopies in studying such complex heterogeneous biomolecular processes, we show the development and application of Infrared Nanospectroscopy (AFM-IR). AFM-IR combines the high spatial resolution of AFM (~1 nm) with the chemical analysis power of infrared (IR) spectroscopy. As major advance in the field, we demonstrate here the achievement of single protein molecule chemical identification and secondary structure determination. We exploit this unprecedented sensitivity to unravel the molecular interaction fingerprint of pathological amyloid with a small molecule capable to prevent neurodegeneration in animal models of disease. Finally, taking inspiration from nature, we prove the application of AFM and AFM-IR to unravel the structure of functional and biocompatible protein self-assemblies as promising candidates for the development of novel class of sustainable biomaterials to substitute fossil fuel based plastics [6-8]. Overall, the aim of our present and future research is to expand the capabilities of nanoscience to open a new window of observation on the fundamental biomolecular processes at the core of life and neurodegeneration; as well as to shed light on the structure-activity relationship of biomolecules, and characterises functional materials for nano- and bio-science applications.
References  Zhuo, ..., Ruggeri*, Dietler*, ACS Nano, 2021.  Ruggeri, ACS Nano, 2020.  Ruggeri, PNAS, 2018.  Ruggeri, Nature Comm., 2020.  Ruggeri, Nature Comm., 2021.  Marchesi, Advanced Functional Materials, 2020.  Shen, Ruggeri, Nature Nanotechnology, 2020.  Qamar*, Wang*, Randle*, Ruggeri*, Cell, 2018.