Scientific publications

Previous work on murine models and humans demonstrated global as well as tissue-specific molecular ageing trajectories of RNAs. Extracellular vesicles (EVs) are membrane vesicles mediating the horizontal transfer of genetic information between different tissues. We sequenced small regulatory RNAs (sncRNAs) in two mouse plasma fractions at five time points across the lifespan from 2–18 months: (1) sncRNAs that are free-circulating (fc-RNA) and (2) sncRNAs bound outside or inside EVs (EV-RNA). Different sncRNA classes exhibit unique ageing patterns that vary between the fcRNA and EV-RNA fractions. While tRNAs showed the highest correlation with ageing in both fractions, rRNAs exhibited inverse correlation trajectories between the EV- and fc-fractions. For miRNAs, the EV-RNA fraction was exceptionally strongly associated with ageing, especially the miR-29 family in adipose tissues. Sequencing of sncRNAs and coding genes in fat tissue of an independent cohort of aged mice up to 27 months highlighted the pivotal role of miR-29a-3p and miR-29b-3p in ageing-related gene regulation that we validated in a third cohort by RT-qPCR

The recent success of mRNA vaccines using lipid-based vectors highlights the importance of strategies for nucleotide delivery under the pandemic situation. Although current mRNA delivery is focused on lipid-based vectors, still they need to be optimized for increasing stability, targeting, and efficiency, and for reducing toxicity. In this regard, other vector systems featuring smart strategies such as pH-responsive degradability and endosomal escape ability hold the potential to overcome the current limitations. Here, we report pH-responsive polymeric nanorods made of amino acid-derivatives connected by dynamic covalent bonds called proteoid-biodynamers, as mRNA vectors. They show excellent biocompatibility due to the biodegradation, and outstanding transfection. The biodynamers of Lys, His, and Arg or monomer mixtures thereof were shown to form nanocomplexes with mRNA. They outperformed conventional transfection agents three times regarding transfection efficacy in three human cell lines, with 82–98% transfection in living cells. Also, we confirmed that the biodynamers disrupted the endosomes up to 10-fold more in number than the conventional vectors. We discuss here their outstanding performance with a thorough analysis of their nanorod structure changes in endosomal microenvironments.

A coupled finite strain chemo-transport-mechanical formulation with trapping is here proposed to extend a previous work set in the realm of small strain theory in continuum mechanics. The theory is rooted in non-equilibrium rational thermodynamics. The kinematics is based on a multiplicative decomposition of the deformation gradient to account for swelling and shrinking, thermal, elastic and inelastic contributions. Mass balance laws and balance of linear and angular momentum, as well as the laws of thermodynamics for a convecting body, are directly formulated in their material description, after specifications of some standard transformation rules between current and reference configuration. Thermodynamic restrictions are identified based on the functional dependence of the referential Helmholtz free energy density, which is chosen as the thermodynamic potential, and further subjected to a constitutive additive decomposition. Constitutive prescriptions for the chemical potentials, referential heat and mass fluxes, chemical kinetics and the generalized heat equation lead to the establishment of the governing equations. The theoretical framework is complemented by numerical simulations, highlighting the potential of the proposed formulation in multi-physics applications.

We review a broad range of topics related to the interplay of electrochemistry and mechanics in all solid-state batteries. The modeling frameworks that exist in the literature are varied in terms of their sophistication and ability to capture critical observations. Modeling frameworks for diffusion induced stress and fracture due to lithiation swelling and shrinkage in storage materials for the cathodes are well-established along with models for lithium-ion transport in solid electrolytes. Similarly, aspects of the effect of stress on the redox reactions at the Li metal/electrolyte interface are well-understood. These models typically modify Butler–Volmer kinetics but neglect the effect of creep or other plastic deformations of the metal electrode on the interface kinetics. Nevertheless, they successfully describe the roughening of the metal electrode/electrolyte interface during deposition or plating. By contrast, Butler–Volmer kinetics accounting only for the interfacial stress are unable to predict voids that have been observed to form in the metal electrode and we discuss a hypothesis that creep deformation of the metal electrode has a more fundamental effect on the redox reactions. Similarly, models for the nucleation and growth of lithium filaments in solid electrolytes are also inconsistent with recent observations which suggest that cracks in solid electrolytes are only partially filled with lithium metal. We conclude by summarizing aspects of the interplay of electrochemistry and mechanics in all solid-state batteries that are well-understood and areas where significant open questions remain.

The most widely-used representation of the compressible, isotropic, neo-Hookean hyperelastic model is considered in this paper. The version under investigation is that which is implemented in the commercial finite element software ABAQUS, ANSYS and COMSOL. Transverse stretch solutions are obtained for the following homogeneous deformations: uniaxial loading, equibiaxial loading in plane stress, and uniaxial loading in plane strain. The ground-state Poisson’s ratio is used to parameterize the constitutive model, and stress solutions are computed numerically for the physically permitted range of its values. Despite its broad application to a number of engineering problems, the physical limitations of the model, particularly in the small to moderate stretch regimes, are not explored. In this work, we describe and analyze results and make some critical observations, underlining the model’s advantages and limitations. For example, a snap-back feature of the transverse stretch is identified in uniaxial compression, a physically undesirable behavior unless validated by experimental data. The domain of this non-unique solution is determined in terms of the ground-state Poisson’s ratio and the state of stretch and stress. The analyses we perform are essential to enable the understanding of the characteristics of the standard, compressible, isotropic, neo-Hookean model used in ABAQUS, ANSYS and COMSOL. In addition, our results provide a framework for the parameter-fitting procedure needed to characterize this standard, compressible, isotropic neo-Hookean model in terms of experimental data.

Secondary particles comprising a large number of nickel-rich single crystal primary particles are extensively used as storage particles in cathodes of lithium-ion batteries. It is well-established that crack formation in secondary particles is an important degradation mode that contributes to decline in battery performance. Recent X-ray tomographic observations suggest that, at very low C-rates, concentration gradients of lithium within an NMC811 secondary particle are negligible yet cracking still occurs. Additionally, during delithiation the primary particles shrink yet a volumetric expansion of the secondary particle occurs. These observations are explained by a numerical model of distributed cracking due to the extreme anisotropy of lithiation strain of primary particles. The incompatible deformation from grain to grain induces large self-stresses even in the absence of spatial gradients in the lithium concentration. The stress state is sufficient to drive a dynamic catastrophic fracture event, and the associated kinetic energy acquired by the primary particles moves them apart (akin to an explosive event) with the carbon and binder domain surrounding each secondary particle restricting the outward motion of the primary particles. It is predicted that a volume expansion of the secondary particles on the order of 20 % accompanies cracking, in agreement with recently reported observations.

Nanoinjection—the process of intracellular delivery using vertically configured nanostructures—is a physical route that efficiently negotiates the plasma membrane, with minimal perturbation and toxicity to the cells. Nanoinjection, as a physical membrane-disruption-mediated approach, overcomes challenges associated with conventional carrier-mediated approaches such as safety issues (with viral carriers), genotoxicity, limited packaging capacity, low levels of endosomal escape, and poor versatility for cell and cargo types. Yet, despite the implementation of nanoinjection tools and their assisted analogues in diverse cellular manipulations, there are still substantial challenges in harnessing these platforms to gain access into cell interiors with much greater precision without damaging the cell’s intricate structure. Here, we propose a non-viral, low-voltage, and reusable electroactive nanoinjection (ENI) platform based on vertically configured conductive nanotubes (NTs) that allows for rapid influx of targeted biomolecular cargos into the intracellular environment, and for successful gene silencing. The localization of electric fields at the tight interface between conductive NTs and the cell membrane drastically lowers the voltage required for cargo delivery into the cells, from kilovolts (for bulk electroporation) to only ≤ 10 V; this enhances the fine control over membrane disruption and mitigates the problem of high cell mortality experienced by conventional electroporation.

Our work presents a high-throughput kinetic killing assay in the 3D matrix using high-content imaging that is a robust and powerful cytotoxicity assay for evaluating the killing efficiency of immune killer cells or conducting drug screening under physiologically and pathologically relevant scenarios, particularly in the context of solid tumors.

Growth constitutes a powerful method to post-modulate materials’ structures and functions without compromising their mechanical performance for sustainable use, but the process is irreversible. To address this issue, we here report a growing-degrowing strategy that enables thermosetting materials to either absorb or release components for continuously changing their sizes, shapes, compositions, and a set of properties simultaneously. The strategy is based on the monomer-polymer equilibrium of networks in which supplying or removing small polymerizable components would drive the networks toward expansion or contraction. Using acid-catalyzed equilibration of siloxane as an example, we demonstrate that the size and mechanical properties of the resulting silicone materials can be significantly or finely tuned in both directions of growth and decomposition. The equilibration can be turned off to yield stable products or reactivated again. During the degrowing-growing circle, material structures are selectively varied either uniformly or heterogeneously, by the availability of fillers. Our strategy endows the materials with many appealing capabilities including environment adaptivity, self-healing, and switchability of surface morphologies, shapes, and optical properties. Since monomer-polymer equilibration exists in many polymers, we envision the expansion of the presented strategy to various systems for many applications.

The need for achieving sustainable technologies has encouraged research on renewable and biodegradable materials for novel products that are clean, green, and environmentally friendly. Nanocellulose (NC) has many attractive properties such as high mechanical strength and flexibility, large specific surface area, in addition to possessing good wet stability and resistance to tough chemical environments. NC has also been shown to easily integrate with other materials to form composites. By combining it with conductive and electroactive materials, many of the advantageous properties of NC can be transferred to the resulting composites. Conductive polymers, in particular poly(3,4-ethylenedioxythiophene:poly(styrene sulfonate) (PEDOT:PSS), have been successfully combined with cellulose derivatives where suspensions of NC particles and colloids of PEDOT:PSS are made to interact at a molecular level. Alternatively, different polymerization techniques have been used to coat the cellulose fibrils. When processed in liquid form, the resulting mixture can be used as a conductive ink. This review outlines the preparation of NC/PEDOT:PSS composites and their fabrication in the form of electronic nanopapers, filaments, and conductive aerogels. We also discuss the molecular interaction between NC and PEDOT:PSS and the factors that affect the bonding properties. Finally, we address their potential applications in energy storage and harvesting, sensors, actuators, and bioelectronics.