Biology subjects

Sankaran, S.

Publications and source records attributed to Sankaran, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Patient-Derived Organoids Functionally Stratify Epithelial Ovarian Cancer into Clinically Relevant Chemotherapy Response Phenotypes

BackgroundOvarian cancer (OC) exhibits substantial heterogeneity in response to platinum-based chemotherapy, resulting in variable clinical outcomes and frequent recurrence. Current biomarkers, including serum CA-125 kinetics and BRCA mutational status, incompletely predict therapeutic response. We investigated whether patient-derived organoids (PDOs) could functionally stratify chemotherapy sensitivity and better reflect patient-specific clinical behaviour. MethodsTwenty patients with OC treated between January 2024 and May 2026 were included, from whom fourteen PDO lines were successfully established. Eight PDOs with robust low-passage expansion and comprehensive longitudinal follow-up underwent functional profiling against carboplatin, paclitaxel, olaparib, and doxorubicin. Drug responses were assessed using half-maximal inhibitory concentration (IC50) and area under the curve (AUC) analyses and integrated with radiological response, serum CA-125 kinetics, BRCA status, and progression-free survival (PFS). ResultsClinical outcomes varied considerably despite similar platinum-taxane regimens. Although post-treatment CA-125 reduction was associated with prolonged PFS, neither CA-125 kinetics nor BRCA mutational status consistently predicted therapeutic response. PDO-guided functional stratification segregated tumours into four clinically relevant platinum-taxane response phenotypes: dual-sensitive, platinum-sensitive/taxane-resistant, platinum-resistant/taxane-sensitive, and dual-resistant. These functional categories closely mirrored radiological response, CA-125 normalisation, and disease progression patterns. PDOs exhibiting low IC50 and AUC values were associated with durable clinical benefit, whereas resistant PDOs tracked with persistent disease and early recurrence. ConclusionsPDO-guided functional stratification captures clinically meaningful therapeutic heterogeneity in OC and complements conventional biomarkers by directly measuring tumour-specific drug susceptibility. Prospective integration of PDO testing may facilitate patient-specific therapeutic selection and support functional precision oncology approaches in ovarian cancer.

Cancer Biology↗

bioRxiv2026

Long-lived yeast-derived lipids promote longevity via regional and systemic metabolic remodeling

Aging is marked by a progressive breakdown of intestinal integrity and metabolic homeostasis, which together drives systemic decline in physiology and reduces lifespan. Here, we found that dietary lipids extracted from a genetically engineered long-lived yeast strain robustly extend lifespan in Drosophila and further uncovered the mechanisms using deuterium oxide-probed stimulated Raman scattering microscopy to image metabolic dynamics and single nucleus RNA sequencing (scRNA-seq) to unveil the underlying pathways. These yeast lipids are enriched in shorter, more saturated fatty acids and phospholipids as revealed by Raman spectroscopy and lipidomics, contributing to increased membrane order and reduced lipid storage. Functionally, targeted dietary supplementation with these lipid components synergistically prolongs fly lifespan. We show that these lipids reverse age-related declines in gut lipid droplet abundance, enhance membrane lipid incorporation, and increase de novo lipid synthesis, thereby improving epithelial structural integrity and barrier function. snRNA-seq identifies transcriptional remodeling in metabolically active enterocytes, including upregulation of autophagy and protein turnover genes, alongside reduction of unsaturated fatty acid biosynthesis. In the brain, dietary lipids orchestrate a dual metabolic strategy--promoting energy conservation and enhanced signaling across most neuronal and glial populations, while selectively boosting mitochondrial function in memory-critical Kenyon cells. All these leads to the enhancement of gut-to-glia communication, particularly through EGFR and FGFR pathways. Finally, analysis of our data with the Fly Metabolic Analysis Pipeline (FLY-MAP) reveals that yeast lipids restructure gut metabolic modules to coordinate energy production, redox balance, and nutrient flexibility. Our study uncovers a cross-kingdom mechanism of metabolic longevity regulation, paving the way for leveraging yeast-derived nutritional components to support tissue homeostasis and promote healthy aging.

molecular biology↗

bioRxiv2026

AGIcam: An open-source IoT-based camera system for automated in-field phenotyping and yield prediction

Continuous, high-frequency monitoring is essential to capture rapid phenological transitions and dynamic crop responses to the environment. However, most phenotyping platforms lack the temporal resolution and automation required for consistent, season-long trait assessment. This study introduces AGIcam, an open-source IoT camera system for automated and continuous in-field plant phenotyping and yield prediction. The platform integrates solar-powered Raspberry Pi units with a modular software stack, comprising Node-RED, InfluxDB, Grafana, and Microsoft Azure, for automated data acquisition, transfer, and visualization. In the 2022 growing season, 18 AGIcam systems were deployed in spring and winter wheat breeding trials, maintaining an uptime of over 85% while capturing frequent RGB and NoIR imagery. Time-series vegetation indices derived from these images were used to predict yield using random forest and Long Short-Term Memory (LSTM) models. The LSTM approach achieved the highest accuracy approximately one week after heading, with mean prediction errors of 3.41% for spring wheat and 1.62% for winter wheat. These results highlight the potential of IoT-based platforms such as AGIcam to enable real-time, scalable, and effective phenotyping solutions for data-driven crop improvement.

plant biology↗

bioRxiv2025

An Engineered Living Material with pro-angiogenic activity inducible by near-infrared light

Impaired angiogenesis is a central barrier in the treatment of chronic and deep tissue wounds, preventing progression through the normal healing cascade. While the combination of near-infrared (NIR) photobiomodulation and pro-angiogenic growth factors has shown synergistic therapeutic benefit, the clinical translation of growth factor therapy is hindered by high cost, instability and the need for localized dosing to avoid aberrant vasculature. Peptidomimetics such as the VEGF-derived QK peptide offer a more stable and predictable alternative, but still require a means for localized, tunable presentation. Here, we establish an engineered living material based delivery system that responds to clinically relevant NIR light to produce and releases a QK-Fusion protein directly at the target site. The probiotic Escherichia coli Nissle 1917 was engineered with an 800 nm-responsive optogenetic circuit and encapsulated within an optimized alginate core-shell hydrogel that ensures biocontainment while allowing controlled outward diffusion of the secreted peptide. The released peptide remains non-cytotoxic and capable of binding extracellular matrix analogs and promoting the formation of organized, branched capillary-like networks in endothelial cultures. We thus establish a strategy for developing engineered living materials towards remote-controlled angiogenic stimulation.

bioengineering↗

bioRxiv2025

RodA Promotes Intestinal Colonization by Group B Streptococcus

BackgroundGroup B Streptococcus (GBS) intestinal colonization is critical for the pathogenesis of late-onset (LO) disease in infants. Using a murine model, we explore the role of rodA, which encodes a peptidoglycan polymerase RodA, belonging to the Shape, Elongation, Division, and Sporulation (SEDS) family that participates in peptidoglycan synthesis and maintenance of cell wall integrity. MethodsWe investigated the contribution of rodA to GBS gastrointestinal (GI) colonization using a wild-type strain (A909 WT) and an isogenic in-frame deletion mutant of rodA (A909{Delta}rodA). Morphological differences between the two strains were examined by transmission electron microscopy (TEM), and the contribution of rodA to GI colonization was assessed in a murine model through monocolonization and cocolonization experiments. We evaluated the growth of the mutant strain under intestinal physiological stress conditions and characterized its interactions with host epithelial cells in vitro. ResultsA909{Delta}rodA showed a unique chaining/aggregation phenotype compared to the A909 WT strain, with the presence of capsule confirmed via TEM and immunoblotting. In murine cocolonization experiments, A909 WT outcompeted A909{Delta}rodA; however, monocolonization experiments exhibited comparable colonization and bacterial burden across the GI tract. In vitro experiments revealed impaired growth in bile and an increase in adhesion to intestinal epithelial cells by the {Delta}rodA mutant. Conclusion(s)rodA plays a role in GBS intestinal colonization. Deletion of rodA increases sensitivity to gastrointestinal stressors in vitro and causes a pronounced defect in competition in vivo, suggesting that the presence of rodA increases the fitness of GBS in the gut.

microbiology↗

bioRxiv2025

Non-conscious Multisensory Integration in the Ventriloquist Effect

The degree to which information from distinct sensory modalities can interact in the absence of conscious awareness remains controversial. According to the Global Neuronal Workspace Theory (GNWT), unconscious sensory information remains relatively confined to sensory cortex and should not be capable of interacting with other modalities until it is broadcast into the (conscious) global workspace comprising late (>300ms) frontal-parietal activation. The ventriloquist effect is a classical multisensory integration phenomenon that refers to the misperception of sound location towards concurrent visual stimulation, such as perceiving the voice of a ventriloquist actor as coming from the moving dummy. Here we used meta-contrast masking to render a brief flash stimulus non-conscious while 30 participants (male, female, and non-binary) performed a sound localization task. We found that, despite being subjectively invisible and at chance at discriminating the flash location, participants were nevertheless biased to localize sounds towards the unconscious flash locations. The effect was present in virtually all participants, was nearly as large as the effect on conscious trials, and was robust to controls for individual differences in task performance. Decoding and ERP analyses of concurrently recorded EEG signals showed that the non-conscious flash location information was present up until around 220ms but not after; suggesting that the visual influence on sound perception may have occurred before conscious broadcast. In support of this, early decoding accuracy on non-conscious trials predicted individual variation in the size of the unconscious ventriloquist effect. Our findings suggest that subjective perception is not required for the integration of signals originating in distinct sensory modalities prompting new questions about the role of subjective perception in multisensory integration.

neuroscience↗

bioRxiv2025

Adaptations of gram-negative and gram-positive probiotic bacteria in engineered living materials

Encapsulation of microbes in natural or synthetic matrices is a key aspect of engineered living materials, although the influence of such confinement on microbial behavior is poorly understood. A few recent studies have shown that spatial confinement and mechanical properties of the encapsulating material significantly influence microbial behavior, including growth, metabolism, and gene expression. While such effects have been shown to elicit various responses in a few micro-organisms like E. coli, yeast, and cyanobacteria, systematic comparative studies between different organisms in the same confinement conditions are missing. Thus, in this study, we report the adaptive responses exhibited by rod-shaped gram-negative and gram-positive probiotic bacteria that are of great interest for developing therapeutic engineered living materials. Accordingly, gram-negative E. coli Nissle 1917 and gram-positive L. plantarum WCFS1 were encapsulated in hydrogel matrices and their growth, metabolic activity, and recombinant gene expression were investigated. By varying the polymer concentration and degree of chemical cross-linking in the hydrogels, it was possible to modulate their stiffness and study how the bacteria adapted to these different confinement conditions. In accordance with previous reports, both bacteria grow from single cells into confined colonies but more interestingly, in E. coli gels, mechanical properties influenced colony growth, size, and morphology, whereas this did not occur in L. plantarum gels. However, with both bacteria, increased matrix stiffness led to higher levels of recombinant protein production within the colonies. By measuring metabolic heat generated in the bacterial gels using a novel isothermal microcalorimetry technique, it was inferred that E. coli adapts to the mechanical restrictions through multiple metabolic transitions and is significantly affected by the different hydrogel properties. Contrastingly, both these aspects were not observed with L. plantarum. These results revealed that despite both these bacteria being gut-adapted probiotics with similar geometries, mechanical confinement affects them considerably differently. The weaker influence of matrix stiffness on L. plantarum is attributed to its slower growth and thicker cell wall possibly enabling the generation of higher turgor pressures to overcome restrictive forces under confinement. By providing fundamental insights into the interplay between mechanical forces and bacterial physiology, this work advances our understanding of how matrix properties shape bacterial behavior. The implications of these findings will aid the design of engineered living materials for therapeutic applications.

biophysics↗

bioRxiv2025

Genetic and materials engineering to enhance inducible gene expression in lactobacilli

Lactiplantibacillus plantarum is known for its potential in healthcare, food production, and environmental biotechnology. However, its broader utility is constrained by a limited genetic toolbox, particularly lacking robust genetic switches for inducible gene expression. Addressing this gap, we developed a novel genetic switch for L. plantarum based on a strong bacteriophage-derived promoter and the food-grade inducer, cumate. However, the switch was susceptible to leaky expression in the late log phase of bacterial growth, which was correlated to a reduction in the culture pH. This leakiness was partially resolved by regulating culture conditions (temperature and nutrients) to limit growth below a certain bacterial density. More interestingly, leaky expression could be stably suppressed by encapsulating the bacteria in alginate as an engineered living material. This physically restricted growth and limited the pHdrop, thereby enhancing the switch performance. The possibilities to regulate protein secretion over several days, reversibly switch protein production, and establish dual functionalities by co-encapsulating strains with different switches were demonstrated. Thus, for the first time, we show a material-based strategy to enhance the performance of a genetic switch in bacteria. This strategy facilitates the development of L. plantarum for advanced applications in biotechnology, pharmaceutics, and living therapeutics.

bioengineering↗

bioRxiv2024

Bacterial Engineered Living Materials modulate Mechanosignaling in Mammalian Cells

Engineered living materials (ELMs) are gaining momentum for biomedical applications as self-replenishing drug depots, smart wound dressings, or as wearable sensors. Current studies on ELM-host interaction are mainly limited to the exchange of biochemical cues between ELMs and surrounding cells and tissues. Here we show that the genetically programmed mechanical properties of ELMs modulate mechanosignaling pathways in mammalian cells cultivated onto the living materials. To this aim, we genetically modulated curli fiber production in E. coli and analyzed the impact on the mechanical properties of the resulting ELMs. The living materials were used as matrix for the cultivation of mammalian cells engineered with a fluorescent reporter to indicate the activation of the mechano-responsive Hippo signaling pathway. We demonstrate that different genetically programmed ELM compositions translated into differential regulation of mechanosignaling in mammalian cells. These findings provide the perspective of using ELMs as extracellular matrix with genetically programmable mechanics for mammalian cells while also highlighting the need to consider the mechanical properties of therapeutic ELMs when assessing interaction with surrounding tissues. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/620857v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@1a1ef9borg.highwire.dtl.DTLVardef@79c49forg.highwire.dtl.DTLVardef@5bb04dorg.highwire.dtl.DTLVardef@193a808_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOToC figureC_FLOATNO C_FIG

bioengineering↗

bioRxiv2024

PEARL: Protein Eluting Alginate with Recombinant Lactobacilli

Engineered living materials (ELMs) made of bacteria in hydrogels have shown considerable promise for therapeutic applications through controlled and sustained release of complex biopharmaceuticals at low costs and with reduced wastage. While most therapeutic ELMs use E. coli due to its large genetic toolbox, most live biotherapeutic bacteria in development are lactic acid bacteria due to native health benefits they offer. Among these, lactobacilli form the largest family of probiotics with therapeutic potential in almost all sites of the body with a microbiome. A major factor limiting the use of lactobacilli in ELMs is their limited genetic toolbox. In this study, we build upon our recent work to expand the genetic programmability of probiotic Lactiplantibacillus plantarum WCFS1 for protein secretion and encapsulate it in a simple, cost-effective, and biocompatible core-shell alginate bead to develop an ELM. We demonstrate the controlled release of recombinant proteins, even up to 14 days from this ELM, thereby terming it PEARL - Protein Eluting Alginate with Recombinant Lactobacilli. Notably, lactobacillus encapsulation offered benefits like bacterial containment, protein release profile stabilization, and metabolite-induced cytotoxicity prevention. These findings demonstrate the mutual benefits of combining recombinant lactobacilli with alginate for the controlled and sustained release of proteins.

bioengineering↗

bioRxiv2024

A screening setup to streamline in vitro Engineered Living Material cultures with the host

Engineered living materials (ELMs), which usually comprise bacteria, fungi, or animal cells entrapped in polymeric matrices, offer limitless possibilities in fields like drug delivery or biosensing. To determine the conditions that sustain ELM performance while ensuring ELM-host compatibility is essential before testing them in vivo. This is critical to reduce animal experimentation and can be achieved through in vitro investigations. Towards this goal, we designed a 96-well plate-based screening method to streamline ELM growth across culture conditions and determine their compatibility potential in vitro. We showed proliferation of three bacterial species encapsulated in hydrogels over time and screened six different cell culture media. We fabricated ELMs in bilayer and monolayer formats and tracked bacterial leakage. After screening, an appropriate medium was selected that sustained growth of an ELM, and it was used to study cytocompatibility in vitro. ELM cytotoxicity on murine fibroblasts and human monocytes was studied by adding ELM supernatants and measuring cell membrane integrity and live/dead staining, respectively, proving ELM cytocompatibility. Our work illustrates a simple setup to streamline the screening of compatible environmental conditions of ELMs with the host.

bioengineering↗

bioRxiv2024

Impact of PI3K pathway alterations on response to immune checkpoint inhibitors in HPV-negative head and neck squamous cell carcinoma

Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway (PI3K pathway) is a major intracellular regulatory pathway commonly involved in cancer survival, proliferation, migration, and metabolism. Activating mutations and amplifications of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) are frequent genomic features of head and neck squamous cell carcinoma (HNSCC). A growing body of evidence suggests that dysregulation of the PI3K pathway suppresses the anti-tumor immune response, thereby enabling tumor immune evasion. We retrospectively analyzed clinicopathologic and genomic data of patients with recurrent or metastatic (R/M) HNSCC treated with immune checkpoint inhibitors (ICI). PI3K pathway alterations were found in 44% and were associated with poor clinical outcomes in the human papillomavirus-negative (HPV-ve) HNSCC patients. PIK3CA expression was found to be inversely correlated with immune gene expression, decreased T-cell infiltration, and reduced CD8 T-cell cytotoxic activity. The pharmacologic inhibition of the PI3K pathway induced an increase in key immune-responsive gene expression in PIK3CA-mutant HPV-ve HNSCC cells. These findings suggest that the PI3K pathway activation promotes immune suppressive phenotype, and playing a role in conferring resistance to immune checkpoint inhibitors in HPV-ve subset of HNSCC patients. HighlightsAlterations in PI3K pathway are associated with poor clinical outcomes in HPV-negative HNSCC patients treated with immune checkpoint therapy. PI3K pathway activation correlates to immune suppressive tumor microenvironment in HNSCC. Pharmacologic inhibition of PI3K induces the expression of interferon-gamma responsive and antigen presentation machinery genes in HNSCC.

cancer biology↗

bioRxiv2024

Single-cell analysis of human diversity in circulating immune cells

Lack of diversity and proportionate representation in genomics datasets and databases contributes to inequity in healthcare outcomes globally1,2. The relationships of human diversity with biological and biomedical phenotypes are pervasive3, yet remain understudied, particularly in a single-cell genomics context. Here we present the Asian Immune Diversity Atlas (AIDA), a multi-national single-cell RNA-sequencing (scRNA-seq) healthy reference atlas of human immune cells. AIDA comprises 1,265,624 circulating immune cells from 619 healthy donors and 6 controls, spanning 7 population groups across 5 countries. AIDA is one of the largest healthy blood datasets in terms of number of cells, and also the most diverse in terms of number of population groups. Though population groups are frequently compared at the continental level, we identified a pervasive impact of sub-continental diversity on cellular and molecular properties of immune cells. These included cell populations and genes implicated in disease risk and pathogenesis as well as those relevant for diagnostics. We detected single-cell signatures of human diversity not apparent at the level of cell types, as well as modulation of the effects of age and sex by self-reported ethnicity. We discovered functional genetic variants influencing cell type-specific gene expression, including context-dependent effects, which were under-represented in analyses of non-Asian population groups, and which helped contextualise disease-associated variants. We validated our findings using multiple independent datasets and cohorts. AIDA provides fundamental insights into the relationships of human diversity with immune cell phenotypes, enables analyses of multi-ancestry disease datasets, and facilitates the development of precision medicine efforts in Asia and beyond.

genomics↗

bioRxiv2024

Thermally activated antibiotic production by probiotic bacteria for pathogen elimination

Peptide drugs have seen rapid advancement in biopharmaceutical development, with over 80 candidates approved globally. Despite their therapeutic potential, the clinical translation of peptide drugs is hampered by challenges in production yields and stability. Engineered bacterial therapeutics is a unique approach being explored to overcome these issues by using bacteria to produce and deliver therapeutic compounds at the body site of use. A key advantage of this technology is the possibility to control drug delivery within the body in real time using genetic switches. However, the performance of such genetic switches suffers when used to control drugs that require post-translational modifications or are toxic to the host. In this study, these challenges were experienced when attempting to establish a thermal switch for the production of a ribosomally synthesized and post-translationally modified peptide antibiotic, darobactin, in probiotic E. coli. These challenges were overcome by developing a thermo-amplifier circuit that combined the thermal-switch with a T7 RNA Polymerase and its promoter that overcame limitations imposed by the host transcriptional machinery due to its orthogonality to it. This circuit enabled production of pathogen-inhibitory levels of darobactin at 40{degrees}C while maintaining leakiness below the detection limit at 37{degrees}C. More impressively, the thermo-amplifier circuit sustained production beyond the thermal induction duration. Thus, raised temperature for 2 h was sufficient for the bacteria to produce pathogen-inhibitory levels of darobactin even in the physiologically relevant simulated conditions of the intestines that include bile salts and low nutrient levels. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/579303v2_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1cdb311org.highwire.dtl.DTLVardef@1a7523aorg.highwire.dtl.DTLVardef@77b68org.highwire.dtl.DTLVardef@136f52b_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

Discovery of a high-performance phage-derived promoter/repressor system for probiotic lactobacillus engineering

BackgroundThe Lactobacillus family comprises many species of great importance for the food and healthcare industries, with numerous strains identified as beneficial for humans and used as probiotics. Hence, there is a growing interest in engineering these probiotic bacteria as live biotherapeutics for animals and humans. However, the genetic parts needed to regulate gene expression in these bacteria remain limited compared to model bacteria like E. coli or B. subtilis. To address this deficit, in this study, we selected and tested several bacteriophage-derived genetic parts with the potential to regulate transcription in lactobacilli. ResultsWe screened genetic parts from 6 different lactobacilli-infecting phages and identified one promoter/repressor system with unprecedented functionality in L. plantarum WCFS1. The phage-derived promoter was found to achieve expression levels nearly 9-fold higher than the previously reported strongest promoter in this strain and the repressor was able to almost completely repress this expression by reducing it nearly 500-fold. ConclusionsThe new parts and insights gained from their engineering will enhance the genetic programmability of lactobacilli for healthcare and industrial applications.

synthetic biology↗

bioRxiv2023

Latitudinal patterns of flowering phenology of three widespread tropical species from public media repositories.

Plant phenology encompasses the study of periodic events in biological life cycles of plants and the influence of seasonal changes in weather and other environmental factors. In order to understand the role of the environment and the changing climate on the life cycle of plants, long-term records are required to establish baselines against which significant future deviations can be discerned. This study aims to analyze the spatial flowering pattern of the plant species -Bombax ceiba, Butea monosperma and Cassia fistula across India, through images uploaded on public media repositories like citizen science portals and social media. Citizen science is rapidly emerging as a reliable source of supplementary scientific information, and can be utilized to understand broad patterns of tree behavior. We found that for all three species, flowering period is longer, and begins earlier in southern latitudes as compared to the northern latitudes. We conclude that publicly available images of flowering trees and citizen science data can be used to supplement existing information on tree phenology across India.

ecology↗

bioRxiv2023

Rheological behavior of Pluronic/Pluronic diacrylate hydrogels used for bacteria encapsulation in living materials

Pluronic (Plu) hydrogels containing Pluronic diacrylate (PluDA) have become popular matrices to encapsulate bacteria in engineered living materials. For this purpose, 30 wt% Plu/PluDA hydrogels with variable fraction of covalently crosslinkable PluDA in the hydrogel composition are used. The degree of covalent crosslinking and the consequent different mechanical properties of the hydrogels have been shown to affect bacteria growth, but a systematic investigation of the mechanical response of the hydrogels is still missing. Here we study the rheological response of 30 wt.% Plu/PluDA hydrogels with increasing PluDA fraction between 0 and 1. We quantify the range of viscoelastic properties that can be covered in this system by varying in the PluDA fraction. We present stress relaxation and creep-recovery experiments, and analyze the variation of the critical yield strain/stress, relaxation and recovery parameters of Plu/PluDA hydrogels as function of the covalent crosslinking degree using the Burgers and Weilbull models. We expect this study to help users of Plu/PluDA hydrogels to estimate the mechanical properties of their systems, and eventually to correlate them with the behaviour of bacteria in future Plu/PluDA devices of similar composition.

bioengineering↗

bioRxiv2022

Plasmonic Stimulation of Gold Nanorods for the Photothermal Control of Engineered Living Materials

Engineered living materials (ELMs) use encapsulated microorganisms within polymeric matrices for biosensing, drug delivery, capturing viruses, and bioremediation. It is often desirable to control their function remotely and in real time. Suitable, genetically engineered microorganisms respond to changes of their environment. Here, we combine this local sensitivity with a nanostructured encapsulation material to sensitize the ELM for infrared light. Previously, blue light has been used to stimulate microorganisms that contain optogenetic modules responsive to those wavelengths without the need for exogenous cofactors. Here, we use plasmonic gold nanorods (AuNR) that have a strong absorption maximum at 808 nm, a wavelength where human tissue is relatively transparent. Biocompatible composites of a Pluronic-based hydrogel and AuNR are prepared without agglomeration; they react to illumination by local heating. We measure a photothermal conversion efficiency of 47 % in transient temperature measurements. Steady-state temperature profiles from local photothermal heating are quantified using infrared photothermal imaging, correlated with measurements inside the gel, and applied to stimulate thermoresponsive bacteria. Using a bilayer ELM construct with the thermoresponsive bacteria and the thermoplasmonic composite gel in two separate but connected hydrogel layers, it is shown that the bacteria can be stimulated to produce a fluorescent protein using infrared light in a spatially controlled manner.

bioengineering↗