Biology subjects

de Boer, J.

Publications and source records attributed to de Boer, J..

9 recordsLinked to original sources

bioRxiv2025

High-Fidelity Tuning of Olfactory Mixture Distances in the Perceptual Space of Smell Through a Community Effort

A central goal in sensory science is to establish quantitative mappings between physical stimuli and perceptual responses. While such mappings are well characterized in vision and audition, they remain poorly defined in olfaction, limiting progress toward understanding the representations of smell. Predicting perceptual similarity between odor mixtures offers a promising route to formalize these relationships. To advance this effort, the DREAM (Dialogue for Reverse Engineering Assessment and Methods) Olfactory Mixtures Prediction Challenge assembled a curated, cross-study dataset describing the similarity of 507 mixture pairs and an unpublished test set of 46 mixture pairs. Teams competed to predict the perceptual similarity of mixture pairs, and then collaborated post-challenge to create an ensemble combining top-performing models that notably improves predictions over the existing state-of-the-art models. Moreover, ensemble model maintains high predictive accuracy in novel validation set. Our model provides a reproducible framework for neuroscientists, chemists, and engineers to compare odor mixtures and provides a foundation for future efforts towards better understanding the olfactory properties of mixtures.

neuroscience↗

bioRxiv2025

Micellangelo: a Generative Model of Cell-Topography Interactions

Understanding how materials influence cell behavior is central to biomaterial engineering, yet experimental approaches are limited by throughput and complexity. Here, we present Micellangelo, a generative AI model that simulates high-resolution fluorescence images of cells cultured on micro-topographical surfaces. By conditioning on surface topographies, Micellangelo generates realistic cell morphologies, enabling in silico exploration of cell-material interactions. We fabricated a dataset of human dermal fibroblasts stained for DNA, F-actin, and the mechanosensitive transcription factor YAP across ten distinct topographies. Micellangelo was trained using the flow matching framework, and demonstrated strong visual and quantitative alignment with real microscopy data in terms of morphology, intensity patterns, and mechanotransductive features. Beyond image generation, we demonstrate two proof-of-concept in silico experiments: tuning the strength of topographical conditioning and perturbing subcellular structures to assess phenotypic consequences. The model captures both topography-induced morphological trends and structure-function relationships such as actin-YAP coupling. These results suggest that Micellangelo functions as a digital twin of experimental cell imaging, taking a step towards a scalable platform for hypothesis generation, virtual screening, and design of biomaterial interfaces. This work bridges the fields of biomaterials and generative modeling, and introduces a generalizable framework for conducting biologically meaningful in silico experiments.

bioengineering↗

bioRxiv2024

Connectivity in the human and the monkey brain probes causal involvement of the fornix in Mild Cognitive Impairment and Alzheimer's Disease

Alzheimers disease (AD) is characterised by memory loss and severe deficits in cognitive function associated with neural degeneration in a network of brain regions. However, little is known about those regions connectivity patterns and how that differs from mild cognitive impairment (MCI) or healthy aging. To address that, we used diffusion-weighted MRI to determine connectivity across 11 key memory-related regions and their unique set of connections (connectivity fingerprints) to 14 white matter (WM) tracts. One WM tract particularly important for memory, and attractive target for therapeutic interventions in AD, is the fornix. However, determining fornix-specific contributions to memory deficits or therapeutic benefits is difficult, partly because the fornix carries numerous subcortical and cortical projections. To explore that, we additionally examined MRI-derived connectivity across homologous structures in non-human primates before and after fornix transections. We report several important findings. First, that connectivity between the hippocampus and the anterior thalamus (ATh) is strongly compromised in cognitive decline, as is fornix integrity. We also found strong reductions in the hippocampus-fornix and ATh-fornix connectivity in AD, demonstrating that fingerprint divergence across groups in hippocampal CA1 and ATh can identify differences between people with AD and MCI. In AD, we observed also elevated connectivity between WM tracts and the hippocampus or the ATh, suggesting a compensatory mechanism, which, importantly, depends on a viable fornix. We finally demonstrate that certain thalamic nuclei and hippocampal subfields link through the retrosplenial cortex in both species, highlighting its potential role as an alternative target for interventions in memory disorders.

neuroscience↗

bioRxiv2020

Topographical biomaterials instruct bacterial surface attachment and the in vivo host-pathogen response

Bio-instructive materials that prevent bacterial biofilm formation and drive an appropriate host immune response have the potential to significantly reduce the burden of medical device-associated infections. Since bacterial surface attachment is known to be sensitive to surface topography, we experimentally survey 2,176 combinatorially generated shapes using an unbiased high-throughput micro topographical screen on polystyrene. This identifies topographies that reduce colonization in vitro by up to 15-fold compared with a flat surface for both motile and non-motile bacterial pathogens. Equivalent reductions are achieved on polyurethane, a polymer commonly used in medical devices. Using machine learning methods, a set of design rules based on generalisable descriptors is established for predicting bacteria-resistant micro topographies. In a murine foreign body infection model, anti-attachment topographies are shown to be refractory to P. aeruginosa and to recruit a productive host response, highlighting the potential of simple topographical patterning of non-eluting implants for preventing medical device associated infections.

microbiology↗

bioRxiv2020

Tendon-derived biomimetic surface topographies induce phenotypic maintenance of tenocytes in vitro

The tenocyte niche contains biochemical and biophysical signals that are needed for tendon homeostasis. The tenocyte phenotype is correlated with cell shape in vivo and in vitro, and shape-modifying cues are needed for tenocyte phenotypical maintenance. Indeed, cell shape changes from elongated to spread when cultured on a flat surface, and rat tenocytes lose the expression of phenotypical markers throughout five passages. We hypothesized that tendon gene expression can be preserved by culturing cells in the native tendon shape. To this end, we reproduced the tendon topographical landscape into tissue culture polystyrene, using imprinting technology. We confirmed that the imprints forced the cells into a more elongated shape, which correlated with the level of Scleraxis expression. When we cultured the tenocytes for seven days on flat surfaces and tendon imprints, we observed a decline in tenogenic marker expression on flat but not on imprints. This research demonstrates that native tendon topography is an important factor contributing to the tenocyte phenotype. Tendon imprints therefore provide a powerful platform to explore the effect of instructive cues originating from native tendon topography on guiding cell shape, phenotype and function of tendon-related cells.

bioengineering↗

bioRxiv2020

Expanding Biomaterial Surface Topographical Design Space through Natural Surface Reproduction

Surface topography guides cell behavior and is a tool to endow biomaterials with bioactive properties. The large number of possible designs makes it challenging to find the optimal surface structure to induce a specific cell response. The TopoChip platform is currently the largest collection of topographies with 2176 in silico designed micro-topographies. Still, it is exploring only a small part of the design space due to the boundary conditions of the design algorithm and the surface engineering strategy. Inspired by the diversity of natural surfaces, we assessed to what extend we could expand the topographical design space and consequently the resulting cellular responses using natural surfaces. To this end, we replicated twenty-six plant and insect surfaces in polystyrene and quantified their surface properties using white light interferometry, image analysis and principle component analysis. Next, we quantified mesenchymal stem cell morphology and the pattern of Pseudomonas aeruginosa colonization and compared it to previous data from TopoChip screens. Our data show that natural surfaces extended the TopoChip design space. Moreover, the natural surfaces induced MSC morphologies and bacterial attachment patterns not previously observed on the TopoChip. In the future, we will train our design algorithms with the results obtained by natural surface imprint experiments to further explore the design space and bio-active properties of surface topography.

cell biology↗

bioRxiv2020

On the correlation between material-induced cell shape and phenotypical response of human mesenchymal stem cells

Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, particularly, on the interface of cells and material of the implants. We defined the phenotypic response of human bone marrow-derived mesenchymal stem cells (hMSCs) to 2176 randomly generated surface topographies by probing basic functions such as migration, proliferation, protein synthesis, apoptosis, and differentiation using quantitative image analysis. Clustering the surfaces into 28 archetypical cell shapes, we found a very strict correlation between cell shape and physiological response and selected seven cell shapes to describe the molecular mechanism leading to phenotypic diversity. Transcriptomics analysis revealed a tight link between cell shape, molecular signatures, and phenotype. For instance, proliferation is strongly reduced in cells with limited spreading, resulting in down-regulation of genes involved in the G2/M cycle and subsequent quiescence, whereas cells with large filopodia are related to activation of early response genes and inhibition of the osteogenic process. Thus, we have started to unravel the open question of how cell function follows cell shape. This will allow designing implants that can actively regulate cellular, molecular signalling through cell shape. Here we are proposing an approach to tackle this question.

bioinformatics↗

bioRxiv2020

Synergistic Material-Topography Combinations to Achieve Immunomodulatory Osteogenic Biomaterials

Human mesenchymal stem cells (hMSCs) are widely represented in ongoing regenerative medicine clinical trials due to their ease of autologous implantation. In bone regeneration, crosstalk between macrophages and hMSCs is critical with macrophages playing a key role in the recruitment and differentiation of hMSCs. However, engineered biomaterials able to both direct hMSC fate and modulate macrophage phenotype have not yet been identified. A novel combinatorial chemistry-microtopography screening platform, the ChemoTopoChip, is used to identify materials suitable for bone regeneration by screening with human immortalized mesenchymal stem cells (hiMSCs) and human macrophages. The osteoinduction achieved in hiMSCs cultured on the "hit" materials in basal media is comparable to that seen when cells are cultured in osteogenic media, illustrating that these materials offer a materials-induced alternative in bone-regenerative applications. These also exhibit immunomodulatory effects, concurrently polarizing macrophages towards a pro-healing phenotype. Control of cell response is achieved when both chemistry and topography are recruited to instruct the required cell phenotype, combining synergistically. The large library of materials reveals that the relative roles of microtopography and material chemistry are similar, and machine learning identifies key material and topographical features for cell-instruction.

bioengineering↗

bioRxiv2020

Surface topography is a context-dependent activator of TGF-β signaling in mesenchymal stem cells

We previously found that surface topographies induce the expression of the Scxa gene, encoding Scleraxis in tenocytes. Because Scxa is a TGF-{beta} responsive gene, we investigated the link between mechanotransduction and TGF-{beta} signaling. We discovered that mesenchymal stem cells exposed to both micro-topographies and TGF-{beta}2 display synergistic induction of SMAD phosphorylation and transcription of the TGF-{beta} target genes SCXA, a-SMA, and SOX9. Pharmacological perturbations revealed that Rho/ROCK/SRF signaling is required for this synergistic response. We further found an activation of the early response genes SRF and EGR1 during the early adaptation phase on micro-topographies, which coincided with higher expression of the TGF-{beta} type-II receptor gene. Of interest, PKC activators Prostratin and Ingenol-3, known for inducing actin reorganization and activation of serum response elements, were able to mimic the topography-induced TGF-{beta} response. These findings provide novel insights into the convergence of mechanobiology and TGF-{beta} signaling, which can lead to improved culture protocols and therapeutic applications.

cell biology↗