Biology subjects

Vu, L. M.

Publications and source records attributed to Vu, L. M..

4 recordsLinked to original sources

bioRxiv2026

Electrodeposited Biocompatible Coatings for 3D Electrodes on Retinal Prostheses

Photovoltaic subretinal prosthesis, PRIMA, provides central vision to patients blinded by age-related macular degeneration, with acuity matching the 100 m pixel size. Further miniaturization requires pillar electrodes to position the stimulating surfaces closer to the inner retinal neurons. While such structures can be electroplated in gold and coated on their tops with SIROF, the exposed gold sidewalls are not biocompatible. Sputtering or atomic layer deposition of protective coatings are unsuitable for selectively passivating the pillar structures without also coating the photosensitive regions and return electrodes of the implant. Here, we present a strategy for biocompatible coating of pillar sidewalls while preserving surrounding implant functionality. The approach combines non-critical photoresist lithography to protect planar return electrodes with electrodeposition of TiO2; or Pt onto gold pillar sidewalls. In-vivo studies demonstrated that both TiO2 and Pt coatings are biocompatible and prevent adverse reactions of the retinal tissue to gold. Since specific capacitance of electroplated TiO2 (25 F/cm2) is much lower than that of Pt (240 F/cm2), the former better limits the current from the side walls and ensures that charge injection occurs predominantly through the pillar tops coated with SIROF (~6 mF/cm2). Electrodeposition, combined with noncritical photolithography provides a scalable wafer-level solution for fabrication of biocompatible three-dimensional electro-neural interfaces, addressing a critical bottleneck in bioelectronics.

bioengineering↗

bioRxiv2026

Titanium and platinum coatings reduce inflammation induced by gold on subretinal prosthesis

Subretinal photovoltaic implants provide central vision to patients blinded by atrophic age-related macular degeneration, with acuity limited by their 100-{micro}m pixels. Higher resolution requires smaller pixels incorporating three-dimensional electrodes, which can be fabricated by gold electroplating. However, the retinal response to exposed gold remains poorly characterized. Here, we evaluated gold biocompatibility on subretinal implants in Royal College of Surgeons rats and compared it with platinum- and titanium-coated surfaces. Although in-vivo optical coherence tomography revealed no overt structural disruption, gold implants induced cellular-scale anomalies, including abnormal morphology of rod bipolar cells, microglial accumulation near the implant, and increased cell death within days after implantation. These effects occurred across flat, pillar, and honeycomb geometries, indicating a material-rather than geometry-dependent response. By contrast, platinum- and titanium-coated implants showed substantially lower loss and morphological disruption of rod bipolar cells, together with markedly reduced microglial activation. These findings indicate that exposed gold surfaces can induce acute retinal inflammation and neuronal loss, whereas conformal platinum or titanium coatings substantially improve biocompatibility. Such coatings enable the development of three-dimensional subretinal prostheses with smaller pixels for improved visual resolution.

bioengineering↗

bioRxiv2025

Combinatorial action of regulatory systems generates colistin heteroresistance

Heteroresistance is a form of antibiotic resistance in which a minor subpopulation of resistant cells coexists with a majority susceptible population. Colistin heteroresistance is common among Enterobacter cloacae clinical isolates, threatens its utility as a last-line therapeutic, and has become a model with which to understand the fundamental bases of heteroresistance. Despite numerous insights, the mechanism by which phenotypic heterogeneity is generated within the population and leads to colistin heteroresistance has been unclear. Here, using a transposon-based mutagenesis screen, we identify the sigma factor {sigma}E as the source of heterogeneity in population-wide colistin resistance levels. Single-cell tracking experiments revealed that {sigma}E is active in only one percent of the population at baseline, and only those cells with active {sigma}E survive colistin exposure. However, {sigma}E expression and population heterogeneity are insufficient for survival, as a mutant lacking the PhoPQ two-component system controlling lipid A modifications necessary for colistin resistance retains heterogeneity but loses colistin resistance. These findings lead to a new paradigm in heteroresistance, where the combinatorial action of multiple regulatory systems, encompassing a heterogeneity generator and a distinct resistance generator, are required to give rise to colistin heteroresistance.

microbiology↗

bioRxiv2024

A novel PhoPQ-potentiated mechanism of colistin resistance impairs membrane integrity in Pseudomonas aeruginosa

Increasing bacterial resistance to colistin, a vital last-resort antibiotic, is an urgent challenge. We previously reported that magnesium sequestration by Candida albicans enables Pseudomonas aeruginosa to become colistin-resistant. Here, we show that Mg{superscript 2} depletion drives P. aeruginosa to evolve greater colistin resistance through genetic changes in lipid A biosynthesis-modification pathways and a putative magnesium transporter. These mutations synergize with the Mg2+-sensing PhoPQ two-component signaling system to remodel lipid A structures of the bacterial outer membrane in previously uncharacterized ways. One predominant mutational pathway relies on early mutations in htrB2, a non-essential gene involved in lipid A biosynthesis, which enhances resistance but compromises outer membrane integrity, resulting in fitness costs and increased susceptibility to other antibiotics. A second pathway achieves increased colistin resistance independently of htrB2 mutations without compromising membrane integrity. In both cases, reduced binding of colistin to the bacterial membrane underlies resistance. Our findings reveal that Mg2+ scarcity unleashes two novel trajectories of colistin resistance evolution in P. aeruginosa. (160)

microbiology↗