Search Results (23)

The classical definition of mechanical work, W = F × D, assumes that work depends solely on force magnitude and displacement, independent of loading rate. However, biological tissues exhibit inherent rate sensitivity—muscles demonstrate velocity-dependent force generation governed by Hill’s force–velocity relationship, while connective tissues and joints show load-rate-dependent stiffness and injury thresholds. These rate effects profoundly influence mechanical work, energy dissipation, and functional outcomes. In this work, we revisit the work–energy framework within biomechanics and biomaterials contexts, combining theoretical models, simulations, and a proposed rate-matched nano–bio indentation experiment to quantify how loading rate modulates energy partitioning between recoverable elastic storage and irreversible viscous dissipation. Our analyses span muscle contraction, viscoelastic tissue mechanics, and nanoparticle–membrane interactions, revealing that rapid loading markedly increases viscous dissipation and total mechanical work, even when peak force and displacement remain constant. We demonstrate that classical quasi-static formulations underestimate energy costs and tissue stresses by neglecting temporal dynamics and nonlinear material responses. Our multi-physics experimental–simulation platform bridges this gap, enabling controlled investigation of rate-dependent biomechanical phenomena at the nano–bio interface. These insights inform biomaterials design by emphasizing rate-matching viscoelastic properties to native tissues and guide experimental biomechanics toward capturing full dynamic histories. This unified framework advances understanding of rate-dependent mechanical work, improving predictive modeling, optimizing therapeutic delivery, and enhancing design in sports science, orthopedics, rehabilitation, and nanomedicine. Full article

Wound and injury healing processes are intricate and multifaceted, involving a sequence of events from coagulation to scar tissue formation. Effective wound management is crucial for achieving favorable clinical outcomes. Understanding the cellular and molecular mechanisms underlying wound healing, inflammation, and regeneration is essential for developing innovative therapeutics. This review explored the interplay of cellular and molecular processes contributing to wound healing, focusing on inflammation, innervation, angiogenesis, and the role of cell surface adhesion molecules. Additionally, it delved into the significance of calcium signaling in skeletal muscle regeneration and its implications for regenerative medicine. Furthermore, the therapeutic targeting of cellular senescence for long-term wound healing was discussed. The integration of cutting-edge technologies, such as quantitative imaging and computational modeling, has revolutionized the current approach of wound healing dynamics. The review also highlighted the role of nanotechnology in tissue engineering and regenerative medicine, particularly in the development of nanomaterials and nano–bio tools for promoting wound regeneration. Moreover, emerging nano–bio interfaces facilitate the efficient transport of biomolecules crucial for regeneration. Overall, this review provided insights into the cellular and molecular mechanisms of wound healing and regeneration, emphasizing the significance of interdisciplinary approaches and innovative technologies in advancing regenerative therapies. Through harnessing the potential of nanoparticles, bio-mimetic matrices, and scaffolds, regenerative medicine offers promising avenues for restoring damaged tissues with unparalleled precision and efficacy. This pursuit marks a significant departure from traditional approaches, offering promising avenues for addressing longstanding challenges in cellular and tissue repair, thereby significantly contributing to the advancement of regenerative medicine. Full article

Understanding both the physicochemical and biological interactions of nanoparticles is mandatory for the biomedical application of nanomaterials. By binding proteins, nanoparticles acquire new surface identities in biological fluids, the protein corona. Various studies have revealed the dynamic structure and nano–bio interactions of the protein corona. The binding of proteins not only imparts new surface identities to nanoparticles in biological fluids but also significantly influences their bioactivity, stability, and targeting specificity. Interestingly, recent endeavors have been undertaken to harness the potential of the protein corona instead of evading its presence. Exploitation of this ‘protein–nanoparticle alliance’ has significant potential to change the field of nanomedicine. Here, we present a thorough examination of the latest research on protein corona, encompassing its formation, dynamics, recent developments, and diverse bioapplications. Furthermore, we also aim to explore the interactions at the nano–bio interface, paving the way for innovative strategies to advance the application potential of the protein corona. By addressing challenges and promises in controlling protein corona formation, this review provides insights into the evolving landscape of the ‘protein–nanoparticle alliance’ and highlights emerging. Full article

The adsorption of biomolecules on nanoparticles’ surface ultimately depends on the intermolecular forces, which dictate the mutual interaction transforming their physical, chemical, and biological characteristics. Therefore, a better understanding of the adsorption of serum proteins and their impact on nanoparticle physicochemical properties is of utmost importance for developing nanoparticle-based therapies. We investigated the interactions between potentially therapeutic proteins, neurotrophin 3 (NT3), brain-derived neurotrophic factor (BDNF), and polyethylene glycol (PEG), in a cell-free system and a retinal pigmented epithelium cell line (ARPE-19). The variance in the physicochemical properties of PEGylated NT3–BDNF nanoparticles (NPs) in serum-abundant and serum-free systems was studied using transmission electron microscopy, atomic force microscopy, multi-angle dynamic, and electrophoretic light scattering. Next, we compared the cellular response of ARPE-19 cells after exposure to PEGylated NT3–BDNF NPs in either a serum-free or complex serum environment by investigating protein release and cell cytotoxicity using ultracentrifuge, fluorescence spectroscopy, and confocal microscopy. After serum exposure, the decrease in the aggregation of PEGylated NT3–BDNF NPs was accompanied by increased cell viability and BDNF/NT3 in vitro release. In contrast, in a serum-free environment, the appearance of positively charged NPs with hydrodynamic diameters up to 900 nm correlated with higher cytotoxicity and limited BDNF/NT3 release into the cell culture media. This work provides new insights into the role of protein corona when considering the PEGylated nano–bio interface with implications for cytotoxicity, NPs’ distribution, and BDNF and NT3 release profiles in the in vitro setting. Full article

The unique nano–bio interfacial phenomena play a crucial role in the biosafety and bioapplications of nanomaterials. As a representative two-dimensional (2D) nanomaterial, molybdenum disulfide (MoS₂) has shown great potential in biological applications due to its low toxicity and fascinating physicochemical properties. This review aims to highlight the nano–bio interface of MoS₂ nanomaterials with the major biomolecules and the implications of their biosafety and novel bioapplications. First, the nano–bio interactions of MoS₂ with amino acids, peptides, proteins, lipid membranes, and nucleic acids, as well as the associated applications in protein detection, DNA sequencing, antimicrobial activities, and wound-healing are introduced. Furthermore, to facilitate broader biomedical applications, we extensively evaluated the toxicity of MoS₂ and discussed the strategies for functionalization through interactions among MoS₂ and the variety of macromolecules to enhance the biocompatibility. Overall, understanding the nano–bio interface interaction of two-dimensional nanomaterials is significant for understanding their biocompatibility and biosafety, and further provide guidance for better biological applications in the future. Full article

Two-dimensional (2D) nanomaterials with chemical and structural diversity have piqued the interest of the scientific community due to their superior photonic, mechanical, electrical, magnetic, and catalytic capabilities that distinguish them from their bulk counterparts. Among these 2D materials, two-dimensional (2D) transition metal carbides, carbonitrides, and nitrides with a general chemical formula of M_n+1X_nT_x (where n = 1–3), together known as MXenes, have gained tremendous popularity and demonstrated competitive performance in biosensing applications. In this review, we focus on the cutting-edge advances in MXene-related biomaterials, with a systematic summary on their design, synthesis, surface engineering approaches, unique properties, and biological properties. We particularly emphasize the property–activity–effect relationship of MXenes at the nano–bio interface. We also discuss the recent trends in the application of MXenes in accelerating the performance of conventional point of care (POC) devices towards more practical approaches as the next generation of POC tools. Finally, we explore in depth the existing problems, challenges, and potential for future improvement of MXene-based materials for POC testing, with the goal of facilitating their early realization of biological applications. Full article

Epigallocatechin gallate (EGCG), a major tea catechin, enhances cellular uptake of magnetic nanoparticles (MNPs), but the mechanism remains unclear. Since EGCG may interact with the 67-kDa laminin receptor (67LR) and epidermal growth factor receptor (EGFR), we investigate whether a receptor and its downstream signaling may mediate EGCG’s enhancement effects on nanoparticle uptake. As measured using a colorimetric iron assay, EGCG induced a concentration-dependent enhancement effect of MNP internalization by LN-229 glioma cells, which was synergistically enhanced by the application of a magnetic field. Transmission electron microscopy demonstrated that EGCG increased the number, but not the size, of internalized vesicles, whereas EGCG and the magnet synergistically increased the size of vesicles. EGCG appears to enhance particle–particle interaction and thus aggregation following a 5-min magnet application. An antibody against 67LR, knockdown of 67LR, and a 67LR peptide (amino acid 161–170 of 67LR) attenuated EGCG-induced MNP uptake by 35%, 100%, and 45%, respectively, suggesting a crucial role of 67LR in the effects of EGCG. Heparin, the 67LR-binding glycosaminoglycan, attenuated EGCG-induced MNP uptake in the absence, but not presence, of the magnet. Such enhancement effects of EGCG were attenuated by LY294002 (a phosphoinositide 3-kinase inhibitor) and Akt inhibitor, but not by agents affecting cGMP levels, suggesting potential involvement of signaling downstream of 67LR. In contrast, the antibody against EGFR exerted no effect on EGCG-enhanced internalization. These results suggest that 67LR may be potentially amenable to tumor-targeted therapeutics. Full article

Molecular-based Fluorescent Organic Nanoparticles (FONs) are versatile light-emitting nano-tools whose properties can be rationally addressed by bottom-up molecular engineering. A challenging property to gain control over is the interaction of the FONs’ surface with biological systems. Indeed, most types of nanoparticles tend to interact with biological membranes. To address this limitation, we recently reported on two-photon (2P) absorbing, red to near infrared (NIR) emitting quadrupolar extended dyes built from a benzothiadiazole core and diphenylamino endgroups that yield spontaneously stealth FONs. In this paper, we expand our understanding of the structure-property relationship between the dye structure and the FONs 2P absorption response, fluorescence and stealthiness by characterizing a dye-related series of FONs. We observe that increasing the strength of the donor end-groups or of the core acceptor in the quadrupolar (D-π-A-π-D) dye structure allows for the tuning of optical properties, notably red-shifting both the emission (from red to NIR) and 2P absorption spectra while inducing a decrease in their fluorescence quantum yield. Thanks to their strong 1P and 2P absorption, all FONs whose median size varies between 11 and 28 nm exhibit giant 1P (10⁶ M⁻¹.cm⁻¹) and 2P (10⁴ GM) brightness values. Interestingly, all FONs were found to be non-toxic, exhibit stealth behaviour, and show vanishing non-specific interactions with cell membranes. We postulate that the strong hydrophobic character and the rigidity of the FONs building blocks are crucial to controlling the stealth nano-bio interface. Full article

The persistency of COVID-19 in the world and the continuous rise of its variants demand new treatments to complement vaccines. Computational chemistry can assist in the identification of moieties able to lead to new drugs to fight the disease. Fullerenes and carbon nanomaterials can interact with proteins and are considered promising antiviral agents. Here, we propose the possibility to repurpose fullerenes to clog the active site of the SARS-CoV-2 protease, M^pro. Through the use of docking, molecular dynamics, and energy decomposition techniques, it is shown that C₆₀ has a substantial binding energy to the main protease of the SARS-CoV-2 virus, M^pro, higher than masitinib, a known inhibitor of the protein. Furthermore, we suggest the use of C₇₀ as an innovative scaffold for the inhibition of SARS-CoV-2 M^pro. At odds with masitinib, both C₆₀ and C₇₀ interact more strongly with SARS-CoV-2 M^pro when different protonation states of the catalytic dyad are considered. The binding of fullerenes to M^pro is due to shape complementarity, i.e., vdW interactions, and is aspecific. As such, it is not sensitive to mutations that can eliminate or invert the charges of the amino acids composing the binding pocket. Fullerenic cages should therefore be more effective against the SARS-CoV-2 virus than the available inhibitors such as masinitib, where the electrostatic term plays a crucial role in the binding. Full article

Nanomedicine against cancer, including diagnosis, prevention and treatment, has increased expectations for the solution of many biomedical challenges in the fight against this disease. In recent decades, an exhaustive design of nanosystems with high specificity, sensitivity and selectivity has been achieved due to a rigorous control over their physicochemical properties and an understanding of the nano–bio interface. However, despite the considerable progress that has been reached in this field, there are still different hurdles that limit the clinical application of these nanosystems, which, along with their possible solutions, have been reviewed in this work. Specifically, physiological processes as biological barriers and protein corona formation related to the administration routes, designing strategies to overcome these obstacles, promising new multifunctional nanotherapeutics, and recent clinical trials are presented in this review. Full article

Molecular dynamics simulations were used to quantitatively investigate the interactions between the twenty proteinogenic amino acids and C₆₀. The conserved amino acid backbone gave a constant energetic interaction ~5.4 kcal mol⁻¹, while the contribution to the binding due to the amino acid side chains was found to be up to ~5 kcal mol⁻¹ for tryptophan but lower, to a point where it was slightly destabilizing, for glutamic acid. The effects of the interplay between van der Waals, hydrophobic, and polar solvation interactions on the various aspects of the binding of the amino acids, which were grouped as aromatic, charged, polar and hydrophobic, are discussed. Although π–π interactions were dominant, surfactant-like and hydrophobic effects were also observed. In the molecular dynamics simulations, the interacting residues displayed a tendency to visit configurations (i.e., regions of the Ramachandran plot) that were absent when C₆₀ was not present. The amino acid backbone assumed a “tepee-like” geometrical structure to maximize interactions with the fullerene cage. Well-defined conformations of the most interactive amino acids (Trp, Arg, Met) side chains were identified upon C₆₀ binding. Full article

The interactions between cells and nanomaterials at the nanoscale play a pivotal role in controlling cellular behavior and ample evidence links cell intercommunication to nanomaterial size. However, little is known about the effect of nanomaterial geometry on cell behavior. To elucidate this and to extend the application in cancer theranostics, we have engineered core–shell cobalt–gold nanoparticles with spherical (Co@Au NPs) and elliptical morphology (Co@Au NEs). Our results show that owing to superparamagnetism, Co@Au NPs can generate hyperthermia upon magnetic field stimulation. In contrast, due to the geometric difference, Co@Au NEs can be optically excited to generate hyperthermia upon photostimulation and elevate the medium temperature to 45 °C. Both nanomaterial geometries can be employed as prospective contrast agents; however, at identical concentration, Co@Au NPs exhibited 4-fold higher cytotoxicity to L929 fibroblasts as compared to Co@Au NEs, confirming the effect of nanomaterial geometry on cell fate. Furthermore, photostimulation-generated hyperthermia prompted detachment of anti-cancer drug, Methotrexate (MTX), from Co@Au NEs-MTX complex and which triggered 90% decrease in SW620 colon carcinoma cell viability, confirming their application in cancer theranostics. The geometry-based perturbation of cell fate can have a profound impact on our understanding of interactions at nano-bio interface which can be exploited for engineering materials with optimized geometries for superior theranostic applications. Full article

Understanding the mechanism of interactions between magnetite nanoparticles and phospholipids that form cellular membranes at the molecular level is of crucial importance for their safe and effective application in medicine (e.g., magnetic resonance imaging, targeted drug delivery, and hyperthermia-based anticancer therapy). In these interactions, their surface coating plays a crucial role because even a small modification to its structure can cause significant changes to the behaviour of the magnetite nanoparticles that come in contact with a biomembrane. In this work, the influence of the magnetite nanoparticles functionalized with native and aminated starch on the thermodynamics, morphology, and dilatational elasticity of the model cell membranes was studied. The model cell membranes constituted the Langmuir monolayers formed at the air–water interface of dipalmitoylphosphatidylcholine (DPPC). The surface of the aminated starch-coated nanoparticles was enriched in highly reactive amino groups, which allowed more effective binding of drugs and biomolecules suitable for specific nano–bio applications. The studies indicated that the presence of these groups also reduced to some extent the disruptive effect of the magnetite nanoparticles on the model membranes and improved their adsorption. Full article

Metal oxide nanoparticles (NPs) have received a great deal of attention as potential theranostic agents. Despite extensive work on a wide variety of metal oxide NPs, few chemically active metal oxide NPs have received Food and Drug Administration (FDA) clearance. The clinical translation of metal oxide NP activity, which often looks so promising in preclinical studies, has not progressed as rapidly as one might expect. The lack of FDA approval for metal oxide NPs appears to be a consequence of the complex transformation of NP chemistry as any given NP passes through multiple extra- and intracellular environments and interacts with a variety of proteins and transport processes that may degrade or transform the chemical properties of the metal oxide NP. Moreover, the translational models frequently used to study these materials do not represent the final therapeutic environment well, and studies in reduced preparations have, all too frequently, predicted fundamentally different physico-chemical properties from the biological activity observed in intact organisms. Understanding the evolving pharmacology of metal oxide NPs as they interact with biological systems is critical to establish translational test systems that effectively predict future theranostic activity. Full article

Every day, new information is presented with respect to how to best combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This manuscript sheds light on such recent findings, including new co-factors (i.e., neuropilin-1) and routes (i.e., olfactory transmucosal) allowing cell entry of SARS-CoV-2 and induction of neurological symptoms, as well as the new SARS-CoV-2 variants. We highlight the SARS-CoV-2 human–animal interfaces and elaborate containment strategies using the same vaccination (i.e., nanoparticle “NP” formulations of the BNT162b2 and mRNA-1273 vaccines) for humans, minks, raccoon dogs, cats, and zoo animals. We investigate the toxicity issues of anti-CoV NPs (i.e., plasmonic NPs and quantum dots) on different levels. Namely, nano–bio interfaces (i.e., protein corona), in vitro (i.e., lung cells) and in vivo (i.e., zebrafish embryos) assessments, and impacts on humans are discussed in a narrative supported by original figures. Ultimately, we express our skeptical opinion on the comprehensive administration of such antiviral nanotheranostics, even when integrated into facemasks, because of their reported toxicities and the different NP parameters (e.g., size, shape, surface charge, and purity and chemical composition of NPs) that govern their end toxicity. We believe that more toxicity studies should be performed and be presented, clarifying the odds of the safe administration of nanotoxocological solutions and the relief of a worried public. Full article