SARS-CoV-2 Omicron Subvariants Do Not Differ Much in Binding Affinity to Human ACE2: A Molecular Dynamics Study.

The emergence of the variant of concern Omicron (B.1.1.529) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exacerbates the COVID-19 pandemic due to its high contagious ability. Studies have shown that the Omicron binds human ACE2 more strongly than the wild type. The prevalence of Omicron in new cases of COVID-19 promotes novel lineages with improved receptor binding affinity and immune evasion. To shed light on this open problem, in this work, we investigated the binding free energy of the receptor binding domain of the Omicron lineages BA.2, BA.2.3.20, BA.3, BA4/BA5, BA.2.75, BA.2.75.2, BA.4.6, XBB.1, XBB.1.5, BJ.1, BN.1, BQ.1.1, and CH.1.1 to human ACE2 using all-atom molecular dynamics simulation and the molecular mechanics Poisson-Boltzmann surface area method. The results show that these lineages have increased binding affinity compared to the BA.1 lineage, and BA.2.75 and BA.2.75.2 subvariants bind ACE2 more strongly than others. However, in general, the binding affinities of the Omicron lineages do not differ significantly from each other. The electrostatic force dominates over the van der Waals force in the interaction between Omicron lineages and human cells. Based on our results, we argue that viral evolution does not further improve the affinity of SARS-CoV-2 for ACE2 but may increase immune evasion.

Theoretical insights into the HO●-induced oxidation of chlorpyrifos pesticide: Mechanism, kinetics, ecotoxicity, and cholinesterase inhibition of degradants.

The oxidation of the common pesticide chlorpyrifos (CPF) initiated by HO● radical and the risks of its degradation products were studied in the gaseous and aqueous phases via computational approaches. Oxidation mechanisms were investigated, including H-, Cl-, CH3- abstraction, HO●-addition, and single electron transfer. In both phases, HO●-addition at the C of the pyridyl ring is the most energetically favorable and spontaneous reaction, followed by H-abstraction reactions at methylene groups (i.e., at H19/H21 in the gas phase and H22/H28 in water). In contrast, other abstractions and electron transfer reactions are unfavorable. However, regarding the kinetics, the significant contribution to the oxidation of CPF is made from H-abstraction channels, mostly at the hydrogens of the methylene groups. CPF can be decomposed in a short time (5-8 h) in the gas phase, and it is more persistent in natural water with a lifetime between 24 days and 66 years, depending on the temperature and HO● concentration. Subsequent oxidation of the essential radical products with other oxidizing reagents, i.e., HO●, NO2●, NO●, and 3O2, gave primary neutral products P1-P15. Acute and chronic toxicity calculations estimate very toxic levels for CPF and two degradation products, P7w and P12w, in aquatic systems. The neurotoxicity of these products was investigated by docking and molecular dynamics. P7w and P12w show the most significant binding scores with acetylcholinesterases, while P8w and P13w are with butyrylcholinesterase enzyme. Finally, molecular dynamics illustrate stable interactions between CPF degradants and cholinesterase enzyme over a 100 ns time frame and determine P7w as the riskiest degradant to the neural developmental system.

Interaction of SARS-CoV-2 with host cells and antibodies: experiment and simulation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the devastating global COVID-19 pandemic announced by WHO in March 2020. Through unprecedented scientific effort, several vaccines, drugs and antibodies have been developed, saving millions of lives, but the fight against COVID-19 continues as immune escape variants of concern such as Delta and Omicron emerge. To develop more effective treatments and to elucidate the side effects caused by vaccines and therapeutic agents, a deeper understanding of the molecular interactions of SARS-CoV-2 with them and human cells is required. With special interest in computational approaches, we will focus on the structure of SARS-CoV-2 and the interaction of its spike protein with human angiotensin-converting enzyme-2 (ACE2) as a prime entry point of the virus into host cells. In addition, other possible viral receptors will be considered. The fusion of viral and human membranes and the interaction of the spike protein with antibodies and nanobodies will be discussed, as well as the effect of SARS-CoV-2 on protein synthesis in host cells.

Identifying inhibitors of NSP16-NSP10 of SARS-CoV-2 from large databases.

The COVID-19 pandemic, which has already claimed millions of lives, continues to pose a serious threat to human health, requiring the development of new effective drugs. Non-structural proteins of SARS-CoV-2 play an important role in viral replication and infection. Among them, NSP16 (non-structured protein 16) and its cofactor NSP10 (non-structured protein 10) perform C2'-O methylation at the 5' end of the viral RNA, which promotes efficient virus replication. Therefore, the NSP16-NSP10 complex becomes an attractive target for drug development. Using a multi-step virtual screening protocol which includes Lipinski's rule, docking, steered molecular dynamics and umbrella sampling, we searched for potential inhibitors from the PubChem and anti-HIV databases. It has been shown that CID 135566620 compound from PubChem is the best candidate with an inhibition constant in the sub-µM range. The Van der Waals interaction was found to be more important than the electrostatic interaction in the binding affinity of this compound to NSP16-NSP10. Further in vitro and in vivo studies are needed to test the activity of the identified compound against COVID-19.Communicated by Ramaswamy H. Sarma.

SARS-CoV-2 Omicron Variant Binds to Human Cells More Strongly than the Wild Type: Evidence from Molecular Dynamics Simulation.

The emergence of the variant of concern Omicron (B.1.1.529) of the severe acute respiratory syndrome coronavirus 2 has aggravated the Covid-19 pandemic due to its very contagious ability. The high infection rate may be due to the high binding affinity of Omicron to human cells, but both experimental and computational studies have yielded conflicting results on this issue. Some studies have shown that the Omicron variant binds to human angiotensin-converting enzyme 2 (hACE2) more strongly than the wild type (WT), but other studies have reported comparable binding affinities. To shed light on this open problem, in this work, we calculated the binding free energy of the receptor binding domain (RBD) of the WT and Omicron spike protein to hACE2 using all-atom molecular dynamics simulation and the molecular mechanics Poisson-Boltzmann surface area method. We showed that Omicron binds to human cells more strongly than the WT due to increased RBD charge, which enhances electrostatic interaction with negatively charged hACE2. N440K, T478K, E484A, Q493R, and Q498R mutations in the RBD have been found to play a critical role in the stability of the RBD-hACE2 complex. The effect of homogeneous and heterogeneous models of glycans coating the viral RBD and the peptidyl domain of hACE2 was examined. Although the total binding free energy is not sensitive to the glycan model, the distribution of per-residue interaction energies depends on it. In addition, glycans have a little effect on the binding affinity of the WT RBD to hACE2.

Determination of Multidirectional Pathways for Ligand Release from the Receptor: A New Approach Based on Differential Evolution.

Steered molecular dynamics (SMD) simulation is a powerful method in computer-aided drug design as it can be used to access the relative binding affinity with high precision but with low computational cost. The success of SMD depends on the choice of the direction along which the ligand is pulled from the receptor-binding site. In most simulations, the unidirectional pathway was used, but in some cases, this choice resulted in the ligand colliding with the complex surface of the exit tunnel. To overcome this difficulty, several variants of SMD with multidirectional pulling have been proposed, but they are not completely devoid of disadvantages. Here, we have proposed to determine the direction of pulling with a simple scoring function that minimizes the receptor-ligand interaction, and an optimization algorithm called differential evolution is used for energy minimization. The effectiveness of our protocol was demonstrated by finding expulsion pathways of Huperzine A and camphor from the binding site of Torpedo California acetylcholinesterase and P450cam proteins, respectively, and comparing them with the previous results obtained using memetic sampling and random acceleration molecular dynamics. In addition, by applying this protocol to a set of ligands bound with LSD1 (lysine specific demethylase 1), we obtained a much higher correlation between the work of pulling force and experimental data on the inhibition constant IC50 compared to that obtained using the unidirectional approach based on minimal steric hindrance.

Amyloid ß Dodecamer Disrupts the Neuronal Membrane More Strongly than the Mature Fibril: Understanding the Role of Oligomers in Neurotoxicity.

The amyloid cascade hypothesis states that senile plaques, composed of amyloid ß (Aß) fibrils, play a key role in Alzheimer's disease (AD). However, recent experiments have shown that Aß oligomers are more toxic to neurons than highly ordered fibrils. The molecular mechanism underlying this observation remains largely unknown. One of the possible scenarios for neurotoxicity is that Aß peptides create pores in the lipid membrane that allow Ca2+ ions to enter cells, resulting in a signal of cell apoptosis. Hence, one might think that oligomers are more toxic due to their higher ability to create ion channels than fibrils. In this work, we study the effect of Aß42 dodecamer and fibrils on a neuronal membrane, which is similar to that observed in AD patients, using all-atom molecular dynamics simulations. Due to short simulation times, we cannot observe the formation of pores, but useful insight on the early events of this process has been obtained. Namely, we showed that dodecamer distorts the lipid membrane to a greater extent than fibrils, which may indicate that ion channels can be more easily formed in the presence of oligomers. Based on this result, we anticipate that oligomers are more toxic than mature fibrils, as observed experimentally. Moreover, the Aß-membrane interaction was found to be governed by the repulsive electrostatic interaction between Aß and the ganglioside GM1 lipid. We calculated the bending and compressibility modulus of the membrane in the absence of Aß and obtained good agreement with the experiment. We predict that the dodecamer will increase the compressibility modulus but has little effect on the bending modulus. Due to the weak interaction with the membrane, fibrils insignificantly change the membrane elastic properties.

Elastic moduli of normal and cancer cell membranes revealed by molecular dynamics simulations.

Recent studies indicate that there are mechanical differences between normal cells and cancer cells. Because the cell membrane takes part in a variety of vital processes, we test the hypothesis of whether or not two fundamental alterations in the cell membrane, i.e., the overexpression of phosphatidylserine lipids in the outer leaflet and a reduction in cholesterol concentration, could cause the softening in cancer cells. Adopting ten models of normal and cancer cell membranes, we carry out 1 µs all-atom molecular dynamics simulations to compare the structural properties and elasticity properties of two membrane types. We find that the overexpression of the phosphatidylserine lipids in the outer leaflet does not significantly alter the area per lipid, the membrane thickness, the lipid order parameters and the elasticity moduli of the cancer membranes. However, a reduction in the cholesterol concentration leads to clear changes in those quantities, especially decreases in the bending, tilt and twist moduli. This implies that the reduction of cholesterol concentration in the cancer membranes could contribute to the softening of cancer cells.

Biorenewable, transparent, and oxygen/moisture barrier nanocellulose/nanochitin-based coating on polypropylene for food packaging applications.

Aluminum-coated polypropylene films are commonly used in food packaging because aluminum is a great gas barrier. However, recycling these films is not economically feasible. In addition, their end-of-life incineration generates harmful alumina-based particulate matter. In this study, coating layers with excellent gas-barrier properties are assembled on polypropylene films through layer-by-layer (LbL) deposition of biorenewable nanocellulose and nanochitin. The coating layers significantly reduce the transmission of oxygen and water vapors, two unfavorable gases for food packaging, through polypropylene films. The oxygen transmission rate of a 60 µm-thick, 20 LbL-coated polypropylene film decreases by approximately a hundredfold, from 1118 to 13.10 cc m-2 day-1 owing to the high crystallinity of nanocellulose and nanochitin. Its water vapor transmission rate slightly reduces from 2.43 to 2.13 g m-2 day-1. Furthermore, the coated film is highly transparent, unfavorable to bacterial adhesion and thermally recyclable, thus promising for advanced food packaging applications.

Nanomechanical Stability of Aß Tetramers and Fibril-like Structures: Molecular Dynamics Simulations.

Alzheimer's disease (AD) is a neurodegenerative disorder and one of the main causes of dementia. The disease is associated with amyloid beta (Aß) peptide aggregation forming initial clusters and then fibril structure and plaques. Other neurodegenerative diseases such as type 2 diabetes, amyotrophic lateral sclerosis, and Parkinson's disease follow a similar mechanism. Therefore, inhibition of Aß aggregation is considered an effective way to prevent AD. Recent experiments have provided evidence that oligomers are more toxic agents than mature fibrils, prompting researchers to investigate various factors that may influence their properties. One of these factors is nanomechanical stability, which plays an important role in the self-assembly of Aß and possibly other proteins. This stability is also likely to be related to cell toxicity. In this work, we compare the mechanical stability of Aß-tetramers and fibrillar structures using a structure-based coarse-grained (CG) approach and all-atom molecular dynamics simulation. Our results support the evidence for an increase in mechanical stability during the Aß fibrillization process, which is consistent with in vitro AFM characterization of Aß42 oligomers. Namely, using a CG model, we showed that the Young modulus of tetramers is lower than that of fibrils and, as follows from the experiment, is about 1 GPa. Hydrogen bonds are the dominant contribution to the detachment of one chain from the Aß fibril fragment. They tend to be more organized along the pulling direction, whereas in the Aß tetramers no preference is observed.

Remdesivir Strongly Binds to Both RNA-Dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations.

The outbreak of a new coronavirus SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) has caused a global COVID-19 (coronavirus disease 2019) pandemic, resulting in millions of infections and thousands of deaths around the world. There is currently no drug or vaccine for COVID-19, but it has been revealed that some commercially available drugs are promising, at least for treating symptoms. Among them, remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to COVID-19 patients in many countries. A recent experiment showed that remdesivir binds to SARS-CoV-2 with an inhibition constant of µM, but the exact target has not been reported. In this work, combining molecular docking, steered molecular dynamics, and umbrella sampling, we examined its binding affinity to two targets including the main protease (Mpro), also known as 3C-like protease, and RdRp. We showed that remdesivir binds to Mpro slightly weaker than to RdRp, and the corresponding inhibition constants, consistent with the experiment, fall to the µM range. The binding mechanisms of remdesivir to two targets differ in that the electrostatic interaction is the main force in stabilizing the RdRp-remdesivir complex, while the van der Waals interaction dominates in the Mpro-remdesivir case. Our result indicates that remdesivir can target not only RdRp but also Mpro, which can be invoked to explain why this drug is effective in treating COVID-19. We have identified residues of the target protein that make the most important contribution to binding affinity, and this information is useful for drug development for this disease.

Emergence of Barrel Motif in Amyloid-ß Trimer: A Computational Study.

Amyloid-ß (Aß) peptides form assemblies that are pathological hallmarks of Alzheimer's disease. Aß oligomers are soluble, mobile, and toxic forms of the peptide that act in the extracellular space before assembling into protofibrils and fibrils. Therefore, oligomers play an important role in the mechanism of Alzheimer's disease. Since it is difficult to determine by experiment the atomic structures of oligomers, which accumulate fast and are polymorphic, computer simulation is a useful tool to investigate elusive oligomers' structures. In this work, we report extended all-atom molecular dynamics simulations, both canonical and replica exchange, of Aß(1-42) trimer starting from two different initial conformations: (i) the pose produced by the best docking of a monomer aside of a dimer (simulation 1), representing oligomers freshly formed by assembling monomers, and (ii) a configuration extracted from an experimental mature fibril structure (simulation 2), representing settled oligomers in equilibrium with extended fibrils. We showed that in simulation 1, regions with small ß-barrels are populated, indicating the chance of spontaneous formation of domains resembling channel-like structures. These structural domains are alternative to those more representative of mature fibrils (simulation 2), the latter showing a stable bundle of C-termini that is not sampled in simulation 1. Moreover, trimer of Aß(1-42) can form internal pores that are large enough to be accessed by water molecules and Ca2+ ions.

Investigation of Binding Affinity between Potential Antiviral Agents and PB2 Protein of Influenza A: Non-equilibrium Molecular Dynamics Simulation Approach.

The PB2 protein of the influenza virus RNA polymerase is a major virulence determinant of influenza viruses. It binds to the cap structure at the 5' end of host mRNA to generate short capped RNA fragments that are used as primers for viral transcription named cap-snatching. A large number of the compounds were shown to bind the minimal cap-binding domain of PB2 to inhibit the cap-snatching machinery. However, their binding in the context of an extended form of the PB2 protein has remained elusive. A previous study reported some promising compounds including azaindole and hydroxymethyl azaindole, which were analyzed here to predict binding affinity to PB2 protein using the steered molecular dynamics (SMD) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods. The results show that the rupture force (Fmax) value of three complexes is in agreement with the binding free energy value (ΔGbind) estimated by the MM-PBSA method, whereas for the non-equilibrium pulling work (Wpull) value a small difference between A_PB2-4 and A_PB2-12 was observed. The binding affinity results indicate the A_PB2-12 complex is more favorable than the A_PB2-4 and A_PB2-16 complexes, which means the inhibitor (12) has the potential to be further developed as anti-influenza agents in the treatment of influenza A.

Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV?

The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, was declared a pandemic by the World Health Organization in March 2020. Genetically, SARS-CoV-2 is closely related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries from 2002 to 2003. Given the significant morbidity and mortality rate, the current pandemic poses a danger to all of humanity, prompting us to understand the activity of SARS-CoV-2 at the atomic level. Experimental studies have revealed that spike proteins of both SARS-CoV-2 and SARS-CoV bind to angiotensin-converting enzyme 2 (ACE2) before entering the cell for replication. However, the binding affinities reported by different groups seem to contradict each other. Wrapp et al. (Science 2020, 367, 1260-1263) showed that the spike protein of SARS-CoV-2 binds to the ACE2 peptidase domain (ACE2-PD) more strongly than does SARS-CoV, and this fact may be associated with a greater severity of the new virus. However, Walls et al. (Cell 2020, 181, 281-292) reported that SARS-CoV-2 exhibits a higher binding affinity, but the difference between the two variants is relatively small. To understand the binding mechnism and experimental results, we investigated how the receptor binding domain (RBD) of SARS-CoV (SARS-CoV-RBD) and SARS-CoV-2 (SARS-CoV-2-RBD) interacts with a human ACE2-PD using molecular modeling. We applied a coarse-grained model to calculate the dissociation constant and found that SARS-CoV-2 displays a 2-fold higher binding affinity. Using steered all-atom molecular dynamics simulations, we demonstrate that, like a coarse-grained simulation, SARS-CoV-2-RBD was associated with ACE2-PD more strongly than was SARS-CoV-RBD, as evidenced by a higher rupture force and larger pulling work. We show that the binding affinity of both viruses to ACE2 is driven by electrostatic interactions.

Computational Model to Unravel the Function of Amyloid-ß Peptides in Contact with a Phospholipid Membrane.

Divalent cations have a strong impact on the properties of phospholipid membranes, where amyloid-ß peptides exert effects related to possible functional or pathological roles. In this work, we use an atomistic computational model of dimyristoyl-phosphatidylcholine (DMPC) membrane bilayers. We perturb this model with a simple model of divalent cations (Mg2+) and with a single amyloid-ß (Aß) peptide of 42 residues, both with and without a single Cu2+ ion bound to the N-terminus. In agreement with the experimental results reported in the literature, the model confirms that divalent cations locally destabilize the DMPC membrane bilayer and, for the first time, that the monomeric form of Aß helps in avoiding the interactions between divalent cations and DMPC, preventing significant effects on the DMPC bilayer properties. These results are discussed in the frame of a protective role of the diluted Aß peptide floating around phospholipid membranes.

Structure and Physicochemical Properties of the Aß42 Tetramer: Multiscale Molecular Dynamics Simulations.

Despite years of intensive research, little is known about oligomeric structures present during Alzheimer's disease (AD). Excess of amyloid beta (Aß) peptides and their aggregation are the basis of the amyloid cascade hypothesis, which attempts to explain the causes of AD. Because of the intrinsically disordered nature of Aß monomers and the high aggregation rate of oligomers, their structures are almost impossible to resolve using experimental methods. For this reason, we used a physics-based coarse-grained force field to extensively search for the conformational space of the Aß42 tetramer, which is believed to be the smallest stable Aß oligomer and the most toxic one. The resulting structures were subsequently optimized, tested for stability, and compared with the proposed experimental fibril models, using molecular dynamics simulations in two popular all-atom force fields. Our results show that the Aß42 tetramer can form polymorphic stable structures, which may explain different pathways of Aß aggregation. The models obtained comprise the outer and core chains and, therefore, are significantly different from the structure of mature fibrils. We found that interaction with water is the reason why the tetramer is more compact and less dry inside than fibrils. Physicochemical properties of the proposed all-atom structures are consistent with the available experimental observations and theoretical expectations. Therefore, we provide possible models for further study and design of higher order oligomers.

Erythromycin, Cethromycin and Solithromycin display similar binding affinities to the E. coli's ribosome: A molecular simulation study.

Macrolide antibiotics bind to the exit tunnel of the ribosome and inhibit protein synthesis blocking its translocation. Thus, antibiotics including the known macrolide Erythromycin (ERY) are active against bacteria. However, at present, some bacteria show resistance to drugs, which requires the development of new powerful antibacterial agents. One possible way is to use the ERY structure, but change its side chains, while the size of the lactone ring can remain unchanged or change. In this work we consider Cethromycin (CET) and Solithromycin (SOL), which are ketolides with quinolylallyl group at C6 and aminophenyl at C11, respectively (both of them have the same lactone ring as ERY). Experiments have shown that these ketolides have improved efficacy against pathogens, but their binding affinity to the E. coli's ribosome is almost identical. To clarify this issue, we have studied in detail the binding mechanisms of ERY, CET and SOL using the docking and molecular dynamic simulations. In agreement with the experiments, we showed that these compounds have similar binding affinities. Desosamine and lactone ring groups play a critical role in the binding of ERY to the ribosome. In CET and SOL, the contribution of keto and alkylaryl groups is balanced by cyclic carbamate. We have demonstrated that increased fluctuations in the ribosomal residues at the binding site led to an increase in the entropic term in the free binding energy of ERY compared to SOL and CET. The alkyl-aryl arm of both ketolides strongly interacts with A752 and U2609. In addition, the presence of macrolides in the exit tunnel can alter the conformation of U2585, which is located in the peptidyl transferase center, through non-bonded interaction. Therefore, the side chain of ketolides affects not only the binding site but also other residues possibly leading to a strong effect on the protein synthesis process. We predict that to combat bacterial mutations, it is necessary either to design a bulk and charged group as a cladinose, or to use several groups with different signs of charges. This prediction can be used for the development of new efficient antibiotics.

The Renewable and Sustainable Conversion of Chitin into a Chiral Nitrogen-Doped Carbon-Sheath Nanofiber for Enantioselective Adsorption.

Well-known hard-template methods for nitrogen (N)-doped chiral carbon nanomaterials require complicated construction and removal of the template, high-temperature pyrolysis, harsh chemical treatments, and additional N-doping processes. If naturally occurring chiral nematic chitin nanostructures [(C8 H13 NO5 )n ] in exoskeletons were wholly transformed into an N-doped carbon, this would be an efficient and sustainable method to obtain a useful chiral nanomaterial. Here, a simple, sacrificial-template-free, and environmentally mild method was developed to produce an N-doped chiral nematic carbon-sheath nanofibril hydrogel with a surface area >300 m2 g-1 and enantioselective properties from renewable chitin biomass. Calcium-saturated methanol physically exfoliated bulk chitin and produced a chiral nematic nanofibril hydrogel. Hydrothermal treatment of the chiral chitin hydrogel at 190 °C produced an N-doped chiral carbon-sheath nanofibril hydrogel without N-doping. This material preferentially adsorbed d-lactic acid over l-lactic acid and produced 16.3 % enantiomeric excess of l-lactic acid from a racemic mixture.

Five different chitin nanomaterials from identical source with different advantageous functions and performances.

Chitin is a renewable and sustainable biomass material that can be converted into various one-dimensional crystalline nanomaterials different in 1) length, 2) diameter, 3) charge density, 4) type of charge, and 5) crystallinity via diverse top-down synthetic methods. These nanomaterials have great potential as sustainable reinforcing and biologically functional materials. The proper design of chitin nanomaterials maximizes their performances in specific applications. Extensive efforts are devoted to understanding each type of chitin nanomaterial produced from different chitin sources; however, few studies have compared different chitin nanomaterials. Herein, we synthesize five different types of chitin nanomaterials from identical sources and compare their physical and chemical properties, including suitability for assorted purposes. Factors 1)-5) are discussed regarding their dominance in determining functionality depending on the specific goals of a) gas barriers, b) mechanical reinforcements, c) dispersibility in various pH aqueous buffers, d) thermal dimensional stability, and e) antibacterial activity. This study gives insights to design new chitin nanomaterial-based materials.

A ball milling-based one-step transformation of chitin biomass to organo-dispersible strong nanofibers passing highly time and energy consuming processes.

Chitin, a sustainable and functional biological macromolecule, can be converted into chitin nanofibers (ChNFs), and are applicable as a mechanically reinforcing and bioactive filler for polymer matrices. Improving the performance of ChNFs typically relies on their nanofibrilization and miscibility with matrices. To transform chitin biomass into organo-dispersible ChNFs, a series of time-/energy-consuming chemical and mechanical treatments are required: 1) deacetylation, 2) disintegration, 3) surface modification to minimize their aggregation through hydrogen bonds, 4) drying, and 5) re-dispersion. This paper presents a one-step method to transform chitin biomass to organo-dispersible acetylated ChNFs via a ball-milling method in the presence of relatively low toxic acetic anhydride without water. This method minimizes water contaminations and energy for dehydrating. The resulting chitin nanofiber material is mixed with poly(l­lactic acid) (PLLA) to produce all-bio-based nanocomposites. The composite indicated a 66% increase in Young's modulus and a 100% increase in tensile strength compared to the pristine PLLA. Furthermore, it did not exhibit any observable cytotoxic effect, thus potentially applicable as a biomedical material.