Biology subjects

Schuerle, S.

Publications and source records attributed to Schuerle, S..

8 recordsLinked to original sources

bioRxiv2026

A modular HaloTag platform for engineering magnetically responsive bacterial microrobots

Functionalizing bacteria with magnetic nanoparticles (MNPs) is a common route toward magnetically responsive bacterial microrobots. However, existing strategies are often limited by low functionalization efficiency, weak binding, poor reproducibility, and nonspecific interactions. Here, we present a robust, specific, and reproducible magnetic functionalization platform based on the self-labeling protein HaloTag, yielding magnetic bacterial microrobots termed HaloBots. Using Escherichia coli as an engineering host, HaloTag was displayed on the outer membrane via the Lpp-OmpA anchoring system, with the assistance of a Long and Flexible (LF) peptide linker. Optimization of genetic engineering vectors and colony purification enabled robust and uniform HaloTag display across bacterial populations. In addition, MNPs were modified with chloroalkane-PEG ligands to enable site-specific covalent conjugation with HaloTag. Tuning the ligand density on MNPs revealed a critical balance between ligand accessibility and surface charge for achieving efficient and specific attachment. Consequently, the resulting HaloBots exhibited stable MNP conjugation and reliable magnetic actuation. Collectively, this work establishes a modular and tunable strategy for engineering magnetically responsive bacterial microrobots.

bioengineering↗

bioRxiv2023

Magnetically Controlled Cyclic Microscale Deformation of in vitro Cancer Invasion Models

Mechanical cues play an important role in the metastatic cascade of cancer. Three-dimensional (3D) tissue matrices with tunable stiffness have been extensively used as model systems of the tumor microenvironment for physiologically relevant studies. Tumor-associated cells actively deform these matrices, providing mechanical cues to other cancer cells residing in the tissue. Mimicking such dynamic deformation in the surrounding tumor matrix may help clarify the effect of local strain on cancer cell invasion. Remotely controlled microscale magnetic actuation of such 3D in vitro systems is a promising approach, offering a non-invasive means for in situ interrogation. Here, we investigate the influence of cyclic deformation on tumor spheroids embedded in matrices, continuously exerted for days by cell-sized anisotropic magnetic probes, referred to as {micro}Rods. Particle velocimetry analysis revealed the spatial extent of matrix deformation produced in response to a magnetic field, which was found to be on the order of 200 {micro}m, resembling strain fields reported to originate from contracting cells. Intracellular calcium influx was observed in response to cyclic actuation, as well as an influence on cancer cell invasion from 3D spheroids, as compared to unactuated controls. Localized actuation at one side of a tumor spheroid tended to result in anisotropic invasion toward the {micro}Rods causing the deformation. In summary, our approach offers a strategy to test and control the influence of non-invasive micromechanical cues on cancer cell invasion and metastasis.

bioengineering↗

bioRxiv2023

Engineering living immunotherapeutic agents for improved cancer treatment

Bacteria-based biohybrid agents are emerging as a promising strategy for cancer therapy due to their ability to actively target tumors, trigger localized inflammation and induce tumor regression. There has been growing interest in using bacteria that are responsive to external cues, such as magnetic fields, to facilitate the formation of robust colonies in tumor the achieve the threshold for clinical efficacy. Several studied have demonstrated the potential of innately magnetically responsive bacteria, known as magnetotactic bacteria (MTB), as steerable agents, however, their immunostimulatory properties and therapeutic effects are yet to be explored. Here, we characterize key properties of human immune cell responses and the behavior of the MTB strain Magnetospirillum magneticum AMB-1 in physiological environments. This work investigates the ability of MTB to maintain magnetic properties, viability in whole blood, cytokine production by macrophages, and the ability to increase uptake of cancer cell material by dendritic cells. This study also explores the use of MTB-liposome complexes for effective delivery of therapeutic payloads. Overall, this study establishes the potential of MTB as a versatile, combined drug delivery platform for immune-mediated cancer therapy.

bioengineering↗

bioRxiv2023

Spatially selective open loop control of magnetic microrobots for drug delivery

Rotating magnetic fields (RMFs), when used to actuate biomedical microrobots for targeted delivery to tumors, have been shown to enable them to overcome physiological barriers and promote their accumulation and penetration into tissue. Nevertheless, directly applying a RMF to a deeply situated target site also leads to off-target actuation in surrounding healthy tissue. Here, we investigate an open-loop control strategy for delivering torque density to diffuse distributions of microrobots at focal points by combining RMFs with magnetostatic gating fields. Taking magnetotactic bacteria (MTB) as a model biohybrid microrobotic system for torque-based actuation, we first use simulation to elucidate off-target torque suppression and find that resolution is set by the relative magnitude of the magnetostatic field and RMF. We study focal torque delivery in vitro, observing off-target suppression of translational velocity of MTB, convection-driven accumulation of companion nanoparticles, and tumor spheroid colonization. We then design, construct, and validate a mouse-scale torque-focusing apparatus incorporating a permanent magnet array, three-phase RMF coils, and offset coils to maneuver the focal point. Our control scheme enables the advantages of torque-based actuation to be combined with spatial targeting, and could be broadly applied to other microrobotic designs for improved drug delivery. One-Sentence SummaryCombining rotating magnetic fields with gating fields enables focused delivery of torque density to dispersed microrobots.

bioengineering↗

bioRxiv2022

Magnetic torque-driven living microrobots for enhanced tumor infiltration

Bacterial microrobots combining self-propulsion and magnetic guidance are increasingly recognized as promising drug delivery vehicles for targeted cancer therapy. Thus far, control strategies have either relied on poorly scalable magnetic field gradients or employed directing magnetic fields with propulsive forces limited by the bacterial motor. Here, we present a magnetic torque-driven actuation scheme based on rotating magnetic fields to wirelessly control Magnetospirillum magneticum AMB-1 bearing versatile liposomal cargo. We observed a 4-fold increase in conjugate translocation across a model of the vascular endothelium and found that the primary mechanism driving this increased transport is torque-driven surface exploration at the cell interface. Using spheroids as a 3D tumor model, fluorescently labeled bacteria colonized their core regions with up to 21-fold higher signal in samples exposed to rotating magnetic fields. In addition to enhanced transport, we demonstrated the suitability of this magnetic stimulus for simultaneous actuation and inductive detection of AMB-1. Finally, we demonstrated that RMF significantly enhances AMB-1 tumor accumulation in vivo following systemic intravenous administration in mice. Our findings suggest that scalable magnetic torque-driven control strategies can be leveraged advantageously with biohybrid microrobots. One-Sentence SummaryMagnetic torque-driven motion enhances infiltration of living microrobots across physiological barriers both in vitro and in vivo.

bioengineering↗

bioRxiv2020

A Possible Inductive Mechanism for Magnetogenetics

Single domain magnetic nanoparticles are increasingly investigated as actuators of biological and chemical processes that respond to externally applied magnetic fields. Although their localized effects are frequently attributed to nanoscale heating, recent experimental evidence casts doubt on the existence of nanoscale temperature gradients in these systems. Here, using the stochastic Landau-Lifshitz-Gilbert equation and finite element modelling, we critically examine an alternative hypothesis that localized effects may be mediated by the induced electric fields arising from the detailed dynamical behavior of individual single domain magnetic particles. We apply our model to two significant case studies of magnetic nanoparticles in alternating magnetic fields: 1) magnetogenetic stimulation of channel proteins associated with ferritin and 2) catalytic enhancement of electrochemical hydrolysis. For the first case, while the local electric fields that ferritin generates are shown to be insufficient to perturb the transmembrane potential, fields on the surface of its mineral core on the order of 102 to 103 V/m may play a role in mass transport or release of iron ions that indirectly lead to stimulation. For the second case, our model indicates electric fields of approximately 300 V/m on the surface of the catalytic particles, with the highest interfacial electric field strengths expected during reversal events. This suggests that the nanoparticles best suited for hysteresis heating would also act as intermittent sources of localized induced electric fields in response to an alternating applied field. Finally, we put the magnitude and timescale of these electric fields in the context of technologically relevant phenomena, showing that they are generally weaker and faster. Popular SummaryThe possibility of using magnetic fields to exert wireless control over biological or chemical processes has stimulated vigorous research efforts across disciplines. Magnetic nanoparticles exposed to alternating magnetic fields have repeatedly been found to exert an influence at the nanoscale, for instance triggering biological responses or regulating chemical catalysis. While these effects have been attributed to nanoscale heating, recent experiments have shown that the temperature in the vicinity of magnetic nanoparticles may not differ appreciably from their surroundings. Could another nanoscale phenomenon be at work? Here, we critically examined the idea that electric fields induced in the immediate vicinity of magnetic nanoparticles might help explain nanoscale effects. The fact that magnetic nanoparticles thermally fluctuate is widely appreciated, but the process that dominates the generation of electric fields is the rapid (typically > 1 GHz) precession that the magnetic moment undergoes during reversal events. Combining a model of the detailed motion of a single magnetic moment with numerical calculation of the induced electric field, we consider the possible role of induced electric fields in two technologically important cases. The first is stimulation of neurons with weakly magnetic ferritin and the second is enhancement of hydrogen production by catalytic magnetic nanoparticles. Understanding the mechanism by which magnetic nanoparticles act on their surroundings is crucial to designing more optimal materials for triggering chemical and biological processes. The role of electric fields explored here also suggests the possibility of pairing magnetic nanoparticles with resonant stimuli to directly drive precession.

neuroscience↗

bioRxiv2020

Magnetospirillum magneticum as a living iron chelator induces transferrin receptor 1 upregulation in cancer cells

Interest has grown in harnessing biological agents for cancer treatment as dynamic vectors with enhanced tumor targeting. While bacterial traits such as proliferation in tumors, modulation of an immune response and local secretion of toxins have been well studied, less is known about bacteria as competitors for nutrients. Here, we investigated the use of a bacterial strain as a living iron chelator, competing for this nutrient vital to tumor growth and progression. We established an in vitro co-culture system consisting of the magnetotactic strain Magnetospirillum magneticum AMB-1 incubated under hypoxic conditions with human melanoma cells. Siderophore production by 108 AMB-1/mL in human transferrin (Tf)-supplemented media was quantified and found to be equivalent to a concentration of 3.78 M {+/-} 0.117 M deferoxamine, a potent drug used in iron chelation therapy. Our experiments revealed an increased expression of transferrin receptor 1 (TfR1) and a significant decrease of cancer cell viability, indicating the bacterias ability to alter iron homeostasis in human melanoma cells. Our results show the potential of a bacterial strain acting as a self-replicating iron-chelating agent, which could serve as an additional mechanism reinforcing current bacterial cancer therapies.

cell biology↗

bioRxiv2019

Genetic encoding of targeted MRI contrast agents for in vivo tumor imaging

Tumor-selective contrast agents have the potential to aid in the diagnosis and treatment of cancer using noninvasive imaging modalities such as magnetic resonance imaging (MRI). Such contrast agents can consist of magnetic nanoparticles incorporating functionalities that respond to cues specific to tumor environments. Genetically engineering magnetotactic bacteria to display peptides has been investigated as a means to produce contrast agents that combine the robust image contrast effects of magnetosomes with transgenic targeting peptides displayed on their surface. This work reports the first use of magnetic nanoparticles that display genetically-encoded pH low insertion peptide (pHLIP), a long peptide intended to enhance MRI contrast by targeting the extracellular acidity associated with the tumors. To demonstrate the modularity of this versatile platform to incorporate diverse targeting ligands by genetic engineering, we also incorporated the cyclic v integrin-binding peptide iRGD into separate magnetosomes. Specifically, we investigate their potential for enhanced binding and tumor imaging both in vitro and in vivo. Our experiments indicate that these tailored magnetosomes retain their magnetic properties, making them well-suited as T2 contrast agents, while exhibiting increased binding compared to wild-type magnetosomes.

synthetic biology↗