Biology subjects

Nelson, B. J.

Publications and source records attributed to Nelson, B. J..

8 recordsLinked to original sources

bioRxiv2026

Dynamic Nanoparticle Assembly-Based Biomedical Microrobots

Precise drug delivery within anatomically complex tissues demands systems capable of both active navigation and deep tissue access, properties that have remained difficult to reconcile in existing nanocarriers and microrobots. Here we introduce Dynabots, a dynamic microrobotic assembly constructed from multifunctional nanoparticles covalently linked by thermally cleavable molecular connectors. This nanoparticle-rich architecture enables the integration of magnetic, imaging, and therapeutic components while preserving a high content of functional material. Collective assembly imparts enhanced magnetic responsiveness and maneuverability, enabling controlled navigation through tortuous biological environments. Upon exposure to mild thermal stimuli, the assemblies undergo programmed disassembly, releasing individual nanoparticles that can diffuse through tissue for localized therapeutic action. We establish the programmable transitions, biocompatibility, and therapeutic efficacy of this process across in vitro and in vivo models, including real-time fluoroscopic guidance within anatomically realistic phantoms and live rodent and porcine systems. By integrating magnetic control, reconfigurable architecture, and stimulus-triggered disassembly, Dynabots unite navigational precision with tissue permeability, providing a versatile platform for adaptive and deep-tissue drug delivery.

bioengineering↗

bioRxiv2024

Magnetoelectric Microrobots for Spinal Cord Injury Regeneration

Regenerative medicine continually seeks effective methods to address spinal cord injuries (SCI), which are known for their limited regenerative potential. Despite advances in neural progenitor cell (NPC) transplants for spinal cord injuries, challenges related to graft survival, reliable in vivo differentiation, and neural integration significantly hinder real functional recovery and limit clinical outcomes. This study introduces NPCbots, biohybrid microrobots engineered by integrating human-induced pluripotent stem cell-derived NPCs with magnetoelectric nanoparticles composed of cobalt ferrite-barium titanate. These enable magnetic navigation and neuronal stimulation, enhancing targeted therapeutic interventions. Our lab-on-a-chip system allows for the mass production of NPCbots, ensuring their differentiation and biocompatibility. Remarkably, in a zebrafish model of SCI, NPCbots stimulated by an alternating magnetic field demonstrated rapid in vivo differentiation and integration into damaged neural pathways, significantly enhancing neural regeneration. Within three days, injured zebrafish treated with NPCbots exhibited almost normal swimming behavior and significantly improved exploratory behavior, showcasing the potential of NPCbots to swiftly repair neural structures and restore the central nervous systems functionality in spinal cord injury models through non-invasive means. Additionally, precise in vitro and in vivo manipulation of NPCbots indicates their broader application in various neurodegenerative disorders, offering a promising route for effective spinal cord and neurological recovery.

neuroscience↗

bioRxiv2022

Optimization of host cell-compatible, antimicrobial peptides effective against biofilms and clinical isolates of drug-resistant bacteria.

Here, we describe the continued synthetic molecular evolution of a lineage of host-compatible antimicrobial peptides (AMP) intended for the treatment of wounds infected with drug-resistant, biofilm-forming bacteria. The peptides tested are variants of an evolved AMP called D-CONGA, which has excellent antimicrobial activities in vitro and in vivo. In this newest generation of rational D-CONGA variants, we tested multiple sequence-structure-function hypotheses that had not been tested in previous generations. Many of the peptide variants have lower antibacterial activity against Gram-positive or Gram-negative pathogens, especially variants that have altered hydrophobicity, secondary structure potential, or spatial distribution of charged and hydrophobic residues. Thus, D-CONGA is generally well tuned for antimicrobial activity. However, we identified a variant, D-CONGA-Q7, with a polar glutamine inserted into the middle of the sequence, that has higher activity against both planktonic and biofilm-forming bacteria as well as lower cytotoxicity against human fibroblasts. Against clinical isolates of K. pneumoniae, innate resistance to D-CONGA was surprisingly common despite a lack of inducible resistance in P. aeruginosa reported previously. Yet, these same isolates were susceptible to D-CONGA-Q7. D-CONGA-Q7 is much less vulnerable to AMP resistance in Gram-negative bacteria than its predecessor. Consistent with the spirit of synthetic molecular evolution, D-CONGA-Q7 achieved a critical gain-of-function and has a significantly better activity profile.

biochemistry↗

bioRxiv2021

Cell Wall Biochemistry Drives Pollen Tube Mechanics and Affects Growth Rate

Pollen tubes maintain cell wall integrity as they rapidly grow towards the ovule, yet need to rupture at a precise moment to release the sperm cells. This biomechanical balance is critical for fertilization and relies on the interplay between turgor pressure and cell wall rigidity. How cell wall composition affects its mechanical properties is, however, not well understood. In this study, we combine experimental and simulation techniques to determine key mechanical parameters using Arabidopsis cell wall mutants. We integrated cellular force microscopy with a Finite Element Method-based model to predict growth rates of different mutant pollen tubes. The Finite Element Method-based model allowed us to quantify the effects of cell wall mutations on the time-independent turgor pressure and cell wall elasticity, while cellular force microscopy enabled determination of time-dependent viscoelastic properties of the cell wall. This novel approach can be applied across biological systems and advances mechanical studies of cell and tissue morphogenesis.

systems biology↗

bioRxiv2021

Growth and immunolocalisation of the brown alga Ectocarpus in a microfluidic environment

PDMS chips have proven to be suitable environments for the growth of several filamentous organisms. However, depending on the specimen, the pattern of growth and cell differentiation has been rarely investigated. We monitored the developmental pattern of the brown alga Ectocarpus inside a PDMS lab-on-chip. Two main methods of inoculation of the lab-on-chip were tested, i.e. by injection of spores or by insertion of sporophyte filaments into the chamber. Growth rate, growth trajectory, cell differentiation, and branching were the main development steps that were monitored for 20 days inside 25 m or 40 m parallel channels under standard light and temperature conditions. They were shown to be similar to those observed in non-constrained in-vitro conditions. Labelling of Ectocarpus cell wall polysaccharides - both with calcofluor for cellulose, and by immunolocalisation for alginates with monoclonal antibodies-showed expected patterns when compared to open space growth using either epifluorescence or confocal microscopy. Overall this article describes the experimental conditions for observing and studying the basic unaltered processes of brown algal growth using microfluidic technology, which provides the basis for future biochemical and biological research.

cell biology↗

bioRxiv2019

The mechanical basis for snapping of the Venus flytrap, Darwin’s ‘most wonderful plant in the world’

The carnivorous Venus flytrap catches prey by an ingenious snapping mechanism. Based on work over the past 190 years, it has become generally accepted that two touches of the traps sensory hairs within 30 seconds, each one generating an action potential, are required to trigger closure of the trap. We developed an electromechanical model which, however, suggests that under certain circumstances one touch is sufficient to generate two action potentials. Using a force-sensing microrobotics system, we precisely quantified the sensory hair deflection parameters necessary to trigger trap closure, and correlated them with the elicited action potentials in vivo. Our results confirm the models predictions, suggesting that the Venus flytrap may be adapted to a wider range of prey movement than previously assumed.

plant biology↗

bioRxiv2019

Complex responses to inflammatory oxidants by the probiotic bacterium Lactobacillus reuteri

Inflammatory diseases of the gut are associated with increased intestinal oxygen concentrations and high levels of inflammatory oxidants, including hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), which are antimicrobial compounds produced by the innate immune system. This contributes to dysbiotic changes in the gut microbiome, including increased populations of pro-inflammatory enterobacteria (Escherichia coli and related species) and decreased levels of health-associated anaerobic Firmicutes and Bacteroidetes. The pathways for H2O2 and HOCl resistance in E. coli have been well-studied, but little is known about how commensal and probiotic bacteria respond to inflammatory oxidants. In this work, we have characterized the transcriptomic response of the anti-inflammatory, gut-colonizing Gram-positive probiotic Lactobacillus reuteri to both H2O2 and HOCl. L. reuteri mounts distinct responses to each of these stressors, and both gene expression and survival were strongly affected by the presence or absence of oxygen. Oxidative stress response in L. reuteri required several factors not found in enterobacteria, including the small heat shock protein Lo18, polyphosphate kinase 2, and RsiR, an L. reuteri-specific regulator of anti-inflammatory mechanisms. These results raise the intriguing possibility of developing treatments for inflammatory gut diseases that could sensitize pro-inflammatory enterobacteria to killing by the immune system while sparing anti-inflammatory, health-associated species.\n\nIMPORTANCEIt is becoming increasingly clear that effective treatment of inflammatory gut diseases will require modulation of the gut microbiota. Preventing pro-inflammatory bacteria from blooming while also preserving anti-inflammatory and commensal species is a considerable challenge, but our results suggest that it may be possible to take advantage of differences in the way different species of gut bacteria resist inflammatory oxidants to accomplish this goal.

microbiology↗

bioRxiv2018

Feeling the force: how pollen tubes deal with obstacles

HighlightPollen tubes literally feel their way through their environment to avoid obstacles as they deliver male gametes to the ovule. We measured their force sensitivity to understand this remarkable behavior.\n\nAbstractPhysical forces are involved in the regulation of plant development and morphogenesis by translating mechanical stress into the modification of physiological processes, which, in turn, can affect cellular growth. Pollen tubes are tip-growing cells that provide an ideal system to study processes induced by exposure to mechanical stress. We combined a lab-on-a-chip device with cellular force microscopy to mimic and quantify the forces that are involved in pollen tube navigation upon confronting mechanical obstacles. Several stages of obstacle avoidance were identified, including force perception, growth adjustment, and penetration. We have experimentally determined the perceptive force, which is the force threshold at which the pollen tube senses the obstacle, for Lilium longiflorum and Arabidopsis thaliana. In addition, we provide evidence that pollen tubes are capable of penetrating narrow gaps by increasing turgor pressure. Taken together, our data indicate that pollen tubes sense physical barriers and actively adjust their growth behavior to overcome them.

plant biology↗