High level research at the nanoscale

Cell wall, especially its peptidoglycan (PG), is the first line of defense for Gram-positive bacteria including multidrug resistant Staphylococcus aureus. Coordinated action of PG synthetases and hydrolases is vital for bacterial growth and viability. While function of several PG synthetases and hydrolases is well understood, the function, regulation, and mechanism of action of PG hydrolases characterized as lysostaphin-like endopeptidases have remained elusive. Many of these M23 family members can hydrolyze glycyl-glycine peptide bonds and show lytic activity against Staphylococcus aureus whose PG contains a pentaglycine bridge, but their exact substrate specificity and hydrolysed bonds are still vaguely determined. In this study, the researchers at NSC have employed NMR spectroscopy to study both the substrate specificity and the bond cleavage of the bactericide lysostaphin and the S. aureus PG hydrolase LytM. Yet, they provide substrate-level evidence for the functional role of these enzymes. Their results show that the specificities of these structurally highly homologous enzymes are similar, but unlike observed earlier both LytM and lysostaphin prefer the D-Ala-Gly cross-linked part of mature peptidoglycan. However, while lysostaphin is genuinely a glycyl-glycine hydrolase, LytM can also act as a D-alanyl-glycine endopeptidase.

L. Antenucci, S. Virtanen, C. Thapa, M. Jartti, I. Pitkänen, H. Tossavainen, and P. Permi. "Reassessing the substrate specificities of the major Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM" eLife, 2024, 13:RP93673.

Figure: Representative examples of real-time NMR monitoring of substrate hydrolysis. Quantitative ¹H spectra at selected time points in the hydrolysis reactions of peptide 2 by lysostaphin (LSS) (A) and LytM (B). In hydrolysis by LSS peaks of Ala Hα in products KdAG and KdAGG gradually appear as a function of time, whereas in LytM reaction KdA and KdAG are formed. Time points are given in minutes next to the spectra. Peak assignments in the reference spectrum are the following: 1 Ala Hα, 2 Gly₁-Gly₄ Hα, 3 Lys Hα, 4 Gly₅ Hα, 5 Lys Hε, 6 Lys Hβ, 7 Lys Hδ, 8 Lys Hγ, 9 Ala Hβ. Asterisk marks the peak of the buffer. The alanine Hα quartets of substrate (4.373 ppm) and KdAGG (4.365 ppm) partially overlap. (C, D) On the left, concentrations in function of reaction time derived from NMR peak integrals from a typical reaction setup with 0.4 mM peptide and 2 μM LSS or 50 μM LytM. On the right, relative product concentrations at reaction end points for the studied peptidoglycan (PG) fragments. This figure was created using BioRender.com.

Researchers at the Nanoscience Center have leveraged machine learning and supercomputer simulations to predict how gold nanoparticles interact with blood proteins. This innovative approach combines extensive molecular dynamics simulations with graph theory and neural networks to identify the most favorable binding sites on proteins such as serum albumin, apolipoprotein E, immunoglobulin E, immunoglobulin G, and fibrinogen. The study revealed that machine learning models, trained on atom-scale simulation data, can accurately predict nanoparticle-protein interactions. This breakthrough opens new avenues for the design of gold nanoparticles as targeted drug delivery systems in precision nanomedicine. The methodology was validated through long-timescale atomistic simulations, confirming its reliability. In a recent computational study, the team demonstrated the potential of functionalized gold nanoparticles to selectively target over-expressed proteins on cancer cell surfaces. This finding underscores the promise of gold nanoparticles in enhancing the efficacy of cancer therapies. The research, supported by the EuroHPC funding program and utilizing the LUMI and Mahti supercomputers, marks a significant step forward in the field of nanomedicine. Future projects will continue to explore the dynamic interactions at the nano-bio interface, aiming to develop advanced diagnostic and therapeutic applications.

M. F. Matus and H. Häkkinen, "Rational Design of Targeted Gold Nanoclusters with High Affinity to Integrin αvβ3 for Combination Cancer Therapy" Bioconjugate Chem. 2024, 35, 10, 1481–1490.

A. Pihlajamäki, M. F. Matus, S. Malola and H. Häkkinen, "GraphBNC: Machine Learning-Aided Prediction of Interactions Between Metal Nanoclusters and Blood Proteins" Adv. Mater. 2024, 2407046.

Researchers have investigated how strong light-matter coupling affects ultra-fast photochemical reactions, specifically the excited-state intra-molecular proton transfer (ESIPT) in 10-hydroxybenzo[h]quinoline (HBQ). Strong coupling between HBQ molecules and confined light modes in optical cavities leads to the formation of polaritons, which can alter photochemistry. However, the origin of this effect remains unclear. Molecular Dynamics (MD) simulations and spectroscopic experiments showed that the rate of ESIPT in coupled HBQ molecules was the same as in uncoupled ones, contradicting theoretical predictions. The disorder among HBQ molecules at room temperature means that the simple model of one-dimensional systems with altered potential energy surfaces is not valid. Instead, the cavity mode is distributed over all eigenstates of the molecule-cavity system, with molecular excitations dominating these states. The results suggest that polaritons act as gateways, funneling excitation from optically bright states into molecular states. This implies that the excitation spectra of HBQ-cavity systems can be predicted by combining the absorption spectrum of the HBQ cavity and the density of molecular states. Experimental confirmation showed that the efficiency of the reaction is controlled by the overlap between bright polaritons and molecular dark states. In conclusion, while strong coupling leads to characteristic Rabi splitting in absorption spectra, thermal disorder smears out the cavity mode excitation, preventing significant perturbation of the potential energy surface and affecting reaction dynamics. These findings provide new insights into the possibilities and limitations of altering chemistry with strong coupling.

A. Dutta, V. Tiainen, I. Sokolovskii, L. Duarte, N. Markešević, D. Morozov, H. A. Qureshi, S. Pikker, G. Groenhof and J. J. Toppari. "Thermal disorder prevents the suppression of ultra-fast photochemistry in the strong light-matter coupling regime." Nat. Commun. 2024, 15, 6600.

Figure: A Potential energy profiles evaluated for intra-molecular proton transfer in the electronic ground state (S₀, black), first electronic excited state (S₁, purple), in the lower polariton (LP), when 256 (orange dashed), 512 (magenta dashed-dotted) or 1024 (blue dotted) identical HBQ molecules are strongly coupled to a single confined light mode of an optical cavity that is resonant with the S₀ → S₁ transition in HBQ. The Rabi splittings are listed in the upper right corner. The energy barrier for proton transfer in the LP state with the highest Rabi splitting is indicated by the double-arrow. B Contribution of the cavity mode to the eigenstates of the coupled HBQ-cavity system with 512 molecules. CSchematic illustration of the cavity geometry (not to scale).

Molecular electronics explores how electrons move through single molecules and how they can be used in electronic circuits. There has been a challenge in aligning the fast time scales used in theoretical models with the slower, more practical time scales seen in experiments. Using a new modeling technique, we studied a setup where a benzenedithiol molecule is connected to copper electrodes and interacts with light in a cavity. Our findings show that this setup produces noticeable light emission and high harmonic generation. Interestingly, the way these effects happen is more similar to what we see in solid-state materials, and the symmetry of the driving field can either suppress or enhance certain light frequencies.

R. Tuovinen and Y. Pavlyukh. Nano Letters 24, 9096 (2024).

Bacteria often sense and respond to their environment by applying sensor histidine kinase proteins. One group of these proteins is bacteriophytochromes, which respond to red/far-red light. They are especially suitable model systems for studying histidine kinase signaling and for optogenetic applications. An international collaboration between the groups of Dr. Heikki Takala from the University of Jyväskylä and Prof. Andreas Möglich from the University of Bayreuth have revealed key details on the regulation of histidine kinase activity. By applying modifications in their bacteriophytochrome-based pREDusk tool, they showed how the delicate balance between two competing enzymatic activities is fine-tuned in histidine kinases. Importantly, they revealed that certain deletions in a so-called ‘linker helix’ within the protein can even reverse its enzymatic activity. The process led to development of an inverted pDERusk tool that, unlike its predecessor, can activate bacterial gene expression under red light.

S.S.M. Meier, E. Multamäki, A.T. Ranzani, H. Takala, and A. Möglich, ”Leveraging the histidine kinase-phosphatase duality to sculpt two-component signaling”, Nat Commun 2024, 15: 4876.

Heat engines are key devices that convert thermal energy into usable energy. Traditional semiconductor-based thermoelectric heat engines freeze out at low temperatures, but in this work we show how a hybrid nanoelectronic system composed of thin layers of ferromagnetic insulators, superconductors, and ferromagnetic metals can operate as a heat engine with a non-vanishing power output even at temperatures below one degree above the absolute zero. Such spintronic heat engines could be used for example as radiation detectors, for deep-space energy harvesting or as a low-temperature thermoelectric memory device.

C. I. Levartoski de Araujo, P. Virtanen, M. Spies, C. González-Orellana, S. Kerschbaumer, M. Ilyn, C. Rogero, T. T. Heikkilä, F. Giazotto and E. Strambini. "Superconducting spintronic heat engine". Nat. Commun. 2024, 15, 4823.

Some viruses, such as the coronavirus that causes COVID-19, can get passed from person to person via contaminated surfaces. But are some surfaces able to reduce the risk of this type of transmission without the help of household disinfectants? As reported in ACS Applied Materials & Interfaces, wood has natural antiviral properties that can reduce the time viruses persist on its surface — and some species of wood are more effective than others at reducing infectivity. Researchers from NSC and University of Eastern Finland looked at how long viruses remained infectious on different species of wood and found that some are promising candidates for sustainable, natural antiviral materials. The publisher also acknowledged the publication by issuing a press release: Wooden surfaces may have natural antiviral properties.

S. Shroff, A. Perämäki, A. Väisänen, P. Pasanen, K. Grönlund, V. H. Nissinen, J. Jänis, A. Haapala, and V. Marjomäki. "Tree Species-Dependent Inactivation of Coronaviruses and Enteroviruses on Solid Wood Surfaces". ACS Appl. Mater. Interfaces 2024, 16, 23, 29621–29633. JYU Press Release.

The manipulation of 2D materials, such as graphene and transition metal dichalcogenides (TMDs), is crucial for the advancement of next-generation electronic, photonic, quantum, and sensor technologies. These materials exhibit unique properties, including high electrical conductivity, mechanical flexibility, and tunable optical characteristics. Traditional processing methods, however, often lack the necessary precision and can introduce thermal damage. This is where ultrafast laser processing comes into play, offering unprecedented control over the material properties at the nanoscale.

Recent advancements in the field of light-matter interactions have paved the way for the transformative use of ultrafast laser processing in 2D materials. A new study conducted by Aleksei Emelianov, Mika Pettersson from the University of Jyväskylä (Finland), and Ivan Bobrinetskiy from Biosense Institute (Serbia), recently published in Advanced Materials as a perspective paper, explores the remarkable potential of ultrafast laser techniques in manipulating 2D layered materials and van der Waals (vdW) heterostructures toward novel applications.

A.V. Emelianov, M. Pettersson and I Bobrinetskiy. "Ultrafast Laser Processing of 2D Materials: Novel Routes toAdvanced Devices" Adv. Mater. 2024, 2402907

Researchers at the University of Jyväskylä and the University of Helsinki have developed a new dissolution approach to recover gold, silver and copper from waste electrical and electronic equipment, and a theoretical model to understand and predict the dissolution process from the atomic scale. The development of new chemical methods is more important than ever because various industrial processes produce waste that cannot be recycled. The experimental work demonstrated the efficiency of the sequential dissolution approach, but it remained unclear how and why different metals are dissolved in a given solvent-oxidant mixtures. The researchers at the Department of Chemistry at the University of Jyväskylä developed a theoretical model, which could explain the experimental results.

A. Zupanc, J. Install, T. Weckman, M. M. Melander, M. J. Heikkilä, M. Kemell, K. Honkala and T. Repo. "Sequential Selective Dissolution of Coinage Metals in Recyclable Ionic Media" Angew. Chem. Int. Ed. 2024, 63, e202407147. JYU Press Release.

In a groundbreaking study, researchers at the NSC together with their international collaborators have discovered that herpesvirus infection instigates a comprehensive remodeling of mitochondrial organization and metabolism within the host cell. This transformation is characterized by significant structural changes, including the emergence of thinner and rougher mitochondria, and functional alterations, such as the thickening and shortening of mitochondrial cristae. The infection also induces a notable increase in the number and area of contact sites between mitochondria and the endoplasmic reticulum, alongside a rise in mitochondrial calcium ion content and proton leak. These findings shed light on the intricate interaction between herpesvirus and host cells, providing valuable insights that could be harnessed for the development of viral treatments.

S. Leclerc, A. Gupta, V. Ruokolainen, J.-H. Chen, K. Kunnas, A. A. Ekman, H. Niskanen, I. Belevich, H. Vihinen, P. Turkki, A. J. Perez-Berna, S. Kapishnikov, E. Mäntylä, M. Harkiolaki, E. Dufour, V. Hytönen, E. Pereiro, T. McEnroe, K. Fahy, M. U. Kaikkonen, E. Jokitalo, C. A. Larabell, V. Weinhardt, S. Mattola, V. Aho, M. Vihinen-Ranta. "Progression of herpesvirus infection remodels mitochondrial organization and metabolism." PLOS Pathogens 20(4): e1011829. JYU Press Release.

The question on the possibility of tuning chemical reactions with the cavity vacuum field has been puzzling physicists and chemists in the recent years. According to most models, the effect seems to vanish due to entropic reasons when a large number of molecules are coupled to the single vacuum field. In the new work, we show how collective effects may after all conspire to go around this effect. Under certain particular conditions, the molecules want to bunch to the same chemical state, leading to a spontaneous symmetry breaking between reactant and product states within the molecular system, and thus the long-time limit of such a stochastic system depends strongly on the initial conditions. We describe the corresponding bifurcation dynamics of the molecular ensemble, and discuss artificial systems beyond molecules, such as collectively coupled flux qubits and cold atom systems, where the effect can be observed."

Kalle S. U. Kansanen and Tero T. Heikkilä, SciPost Phys. 16, 025 (2024)

Our theoretical research shows how junctions between superconductors exhibit a non-reciprocal microwave response, where small signals move differently in forward and backward directions. This non-reciprocity appears due to the presence of bound states in systems with more than two superconductors joining together in a small area called a weak link. Our work lays the basis of evaluating the microwave properties of such bound states and shows the conditions for obtaining a strong non-reciprocal response. Such response is of special interest in quantum signal processing where signal from qubits needs to be routed to the measurement circuit without the corresponding measurement noise coupling back to the qubits. Previously this task has been accomplished with bulky macroscopic scale circulators. We propose such circulators to be replaced by tiny on-chip multiterminal superconducting junctions with much smaller footprint. 

Pauli Virtanen and Tero T. Heikkilä, Physical Review Letters 132, 046002 (2024)

Marjomäki group is currently developing anti-viral surfaces to decrease the spread of infectious diseases. A study published now in Microbiology spectrum found that a resin ingredient is effective against coronaviruses and strongly decreases their infectivity on plastic surfaces. The functionalized surface was effective against both the seasonal human coronavirus and the SARS-CoV-2 virus within 15 min time whereas un-functionalized plastic allowed viruses stay infective at least for 2 days. Structural and biochemical studies showed that the leaching resin component prevented fusion of the virions inside cellular structures. The research is part of the BIOPROT project (Development of bio-based and antimicrobial materials and use as protective equipment) funded by Business Finland and has been done in collaboration with the Finnish company Premix Oy.

S. Shroff, M. Haapakoski, K. Tapio, M. Laajala, M. Leppänen, Z. Plavec, A. Haapala, S. J. Butcher, J. Ihalainen, J. J. Toppari, V. Marjomäki, Microbiology Spectrum, 16.1.2024