Practical guide to single-protein AFM nanomechanical spectroscopy mapping: insights and pitfalls as unraveled by all-atom MD simulations on immunoglobulin G
EntityUAM. Departamento de Física Teórica de la Materia Condensada
PublisherAmerican Chemical Society
10.1021/acssensors.0c02241ACS Sensors 6.2 (2021): 553-564
Funded byJ.G.V. acknowledges funding from a Marie Sklodowska-Curie Fellowship within the Horizon 2020 framework (Grant No. DLV-795286) and the Swiss National Science Foundation (Grant No. CRSK-2 190731/1). R.P. acknowledges support from the Spanish MINECO (Grant No. MAT2017-83273-R) and from the Ministerio de Ciencia e Innovación (MICINN) through the “María de Maeztu” Programme for Units of Excellence in R&D (Grant No. CEX2018-000805-M). R.G. acknowledges funding from the MICINN (Grant No. PID2019-106801GB-I00) and Comunidad de Madrid Grant No. S2018/NMT-4443 (Tec4Bio-CM). We thankfully acknowledge the computer resources, technical expertise, and assistance provided by the Red Española de Supercomputación (RES) at the Minotauro and CTE-Power9 supercomputers (BSC, Barcelona). We thank Dr. Alejandro Martín-González for fruitful discussions
ProjectGobierno de España. MAT2017-83273-R; Gobierno de España. CEX2018-000805-M; Gobierno de España. PID2019-106801GB-I00; Info:eu-repo/grantAgreement/EC/H2020/795286//EU//MolNanoTribology; Comunidad de Madrid. S2018/NMT-4443/Tec4Bio-CM
SubjectsYoung modulus; Mechanical response; Atomic force microscopy; Molecular dynamics; Antibodies; Immunoglobulin; Hydration layers; Física
Rights© 2021 American Chemical Society
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Atomic force microscopy is an invaluable characterization tool in almost every biophysics laboratory. However, obtaining atomic/sub-nanometer resolution on single proteins has thus far remained elusive - a feat long achieved on hard substrates. In this regard, nanomechanical spectroscopy mapping may provide a viable approach to overcome this limitation. By complementing topography with mechanical properties measured locally, one may thus enhance spatial resolution at the single-protein level. In this work, we perform all-atom molecular dynamics simulations of the indentation process on a single immunoglobulin G (IgG) adsorbed on a graphene slab. Our simulations reveal three different stages as a function of strain: a noncontact regime - where the mechanical response is linked to the presence of the water environment - followed by an elastic response and a final plastic deformation regime. In the noncontact regime, we are able to identify hydrophobic/hydrophilic patches over the protein. This regime provides the most local mechanical information that allows one to discern different regions with similar height/topography and leads to the best spatial resolution. In the elastic regime, we conclude that the Young modulus is a well-defined property only within mechanically decoupled domains. This is caused by the fact that the elastic deformation is associated with a global reorganization of the domain. Differences in the mechanical response are large enough to clearly resolve domains within a single protein, such as the three subunits forming the IgG. Two events, unfolding or protein slipping, are observed in the plastic regime. Our simulations allow us to characterize these two processes and to provide a strategy to identify them in the force curves. Finally, we elaborate on possible challenges that could hamper the interpretation of such experiments/simulations and how to overcome them. All in all, our simulations provide a detailed picture of nanomechanical spectroscopy mapping on single proteins, showing its potential and the challenges that need to be overcome to unlock its full potential
Google Scholar:Vilhena Albuquerque D'Orey, José Guilherme - Ortega, Maria - Uhlig, Manuel R. - Garcia, Ricardo - Pérez Pérez, Rubén
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