Biology subjects

Jauffred, L.

Publications and source records attributed to Jauffred, L..

8 recordsLinked to original sources

bioRxiv2026

Pushing for survival: Spatial intermixing and indirect resistance enable collective growth

The survival of bacterial communities depends on complex dynamics at molecular, cellular, and ecosystem levels. Understanding antibiotic resistance requires a broader community context, as emergent dynamics can lead to unexpected outcomes, such as the persistence of susceptible populations or community collapse. We capture these behaviors by integration of microscopy and mathematical modeling to understand how bacterial interactions and spatial organization shape bacteriostatic antibiotic resistance in a two-strain community. We show that local chloramphenicol detoxification and mechanical pushing shape bacterial coexistence and spatial organization, promoting the survival and growth of otherwise susceptible bacteria. Additionally, the timing of antibiotic administration critically determines the growth dynamics, co-existence, local diversity of susceptible and resistant bacteria, and overall community resistance. Together, these insights highlight how community-level interactions fundamentally reshape antibiotic responses and open new avenues to understand and control bacterial resilience. SIGNIFICANCE STATEMENTAntibiotic resistance is usually treated as a property of individual bacterial strains, yet bacteria typically grow in dense, spatially structured communities where physical interactions matter. We find that under bacteriostatic (growth pausing) antibiotic stress, resistant bacteria can create highly localized protective environments that allow sensitive cells to survive and proliferate. This protection arises not only from antibiotic detoxification, but also from growth-driven mechanical pushing that maintains close cell-cell proximity. As a result, antibiotic tolerance emerges as a collective, spatially dependent property rather than an intrinsic trait of single cells. These findings show that spatial organization, physical forces, and treatment timing can strongly reshape therapy outcomes, with implications for how resistance is understood and managed in microbial communities.

biophysics↗

bioRxiv2025

Wrinkles emerge from matrix complementarity in heterogenous biofilms

Biofilms are dynamic communities of microorganisms encased in a self-produced extracellular matrix. These resilient structures pose challenges across nearly all human activities, from healthcare to industry. The mechanical behaviour of a biofilm is shaped by the heterogenous composition of its matrix, both spatially and chemically. In turn, these mechanics influence the biofilms architecture at micro- and macroscopic scales, driving its complexity and adaptability. Morphologically, this is reflected in mechanical deformations of the biofilm known as wrinkles. In nature, biofilms often host different species of bacteria, allowing for a great diversity of matrix components. Here, we use a combination of two Escherichia coli strains as a model for a multispecies biofilm in which each bacterial strain produces one of two complementary matrix fibres: an amyloid protein (curli) or a polysaccharide (phosphoethanolamine-cellulose). Using fluorescence microscopy, we confirm that the two bacterial strains rapidly segregate into isogenic sectors, decreasing local heterogeneity. Furthermore, we show how wrinkles form, both in the homogenous central region of the biofilm, as well as at the boundary between sectors (i.e. where the two matrix producers co-localize). Finally, we show that increasing strain intermixing via the addition of bacteriophages results in thicker, taller wrinkles, irrespective of whether the two fibres are produced by two different strains or co-produced by the same bacteria.

biophysics↗

bioRxiv2024

Tumor Spheroid Uptake of Fluorescent Nanodiamonds is Limited by Mass Density: a 4D Light-Sheet Assay

Fluorescent nanodiamonds (FNDs) with nitrogen-vacancy centers are promising candidates for long-term biolabeling and biosensing applications due to their biocompatibility and unique optomagnetic properties. The employment of nanomaterials in cancer therapy and diagnostics, requires a deep understanding of how nanoparticles (NPs) interact with the three-dimensional (3D) tumor environment. We developed a novel approach, the "Tumor-in-a-Tube" platform, using 4D light-sheet microscopy to explore the spatio-temporal dynamics of FNDs with 3D tumor spheroids. By monitoring the real-time NP sedimentation, spheroid penetration, and cellular uptake of FNDs and polystyrene nanoparticles (PNPs), we marked the impact of NP mass density on their spheroid interaction. Unlike PNPs, higher-density FNDs underwent rapid sedimentation, which minimized their effective concentration and hindered the FND - spheroid interactions. This results in constrained intratumoral accumulation, and size-independent uptake and penetration. Longer FND effective-exposure-time promotes size-dependent cell uptake, verified by FND treatment on 2D monolayers. Nonetheless, FNDs exhibited good biocompatibility and long-term spheroid labeling, allowing for cell isolation from different spheroid layers. Our results suggest the need for NP effective-exposure-time calibration in comparative NP assays, in 3D static models. Overall, our platform provides a valuable tool for bridging the gap between 2D and 3D static models in NP assessment, drug delivery, toxicology profiling and translational research.

biophysics↗

bioRxiv2024

Cell aspect ratio is a mechanical winning strategy in microbial competition

Bacterial competition shapes community architecture, yet a universally conserved determinant remains elusive. We show that cell aspect ratio -a simple morphological feature- confers a competitive advantage. Using growth-based range expansion experiments, we show that longer bacteria conquer the expanding front, even when initially in minority. Using an agent-based model of dividing bacteria, to isolate the effect of aspect ratio, we reveal that the takeover mechanism is collective alignment: groups of locally aligned bacteria form "nematic arms" bridging the central region of the colony to the expanding front. Once at the front, bacteria align parallel to it and block shorter bacteria from access to nutrients and space. We confirm this observation with single-cell experiments and further generalise our findings by introducing a generic continuum model of alignment-dominated competition, explaining both experimental and cell-based model observations. Moreover, we extend our predictions to spherical range expansions and confirm the competitive advantage, even though the effect is less pronounced than in surface-attached colonies. Our results uncover a simple, yet hitherto overlooked, mechanical mechanism determining the outcome of bacterial competition, which is potentially ubiquitous among various bacteria. Current advances in genetic engineering enable aspect ratio tuning as a mechanism with broad implications for biofilm control.

biophysics↗

bioRxiv2023

Genetic mixing and demixing on expanding spherical frontiers

Genetic fluctuation during range expansion is a key process driving evolution. When a bacterial population is expanding on a 2D surface, random fluctuations in the growth of the pioneers at the front line cause a strong de-mixing of genotypes. Even when there is no selective advantage, sectors of low genetic diversity are formed. Experimental studies of range expansions in surface-attached colonies of fluorescently-labeled microorganisms have contributed significantly to our understanding of fundamental evolutionary dynamics. However, experimental studies on genetic fluctuations in 3D range expansions have been sparse, despite their importance for tumour or biofilm development. We encapsulated populations of two fluorescent Escherichia coli strains in inoculation droplets (volumes [~]0.1 nl). The confined ensemble of cells grew when embedded in a hydrogel - with nutrients - and developed 3D colonies with well-defined, sector-like regions. Using a confocal laser scanning microscope (CLSM), we imaged the development of 3D colonies and the emergence of sectors. We characterised how cell concentration in the inoculation droplet controls sectors, growth rate, and the transition from branched colonies to quasi-spherical colonies. We further analysed how sectors on the surface change over time. We complement these experimental results with a modified 3D Eden growth model. The model in 3D spherical growth predicts a phase, where sectors are merging, followed by a steady increase (constant rate), and the experimentally analysed sectors were consistent with this prediction. Ergo, our results demonstrate qualitative differences between radial (2D) and spherical (3D) range expansions and their importance in gene fixation processes.

biophysics↗

bioRxiv2022

Motility mediates satellite formation in confined biofilms

Bacteria have spectacular survival capabilities and can spread in many, vastly different environments. For instance, when pathogenic bacteria infect a host, the cells expand through proliferation and squeezing through narrow pores and elastic matrices. However, the exact role of surface structures and matrix elasticity in colony expansion and morphogenesis is still largely unknown. Here we show how satellite colonies emerge around biofilms embedded in semi-soft agar in controlled in vitro assays. We tested how extra-cellular structures - important for biofilm formation and motility - control this morphology. Moreover, we identify the range of extra-cellular matrix elasticity, where this morphology is possible. When paralleled with mathematical modelling, our results demonstrate that satellite formation allows bacterial communities to spread faster. We anticipate that this strategy is important to speed up expansion in various environments while retaining the close interactions and protection provided by the community.

biophysics↗

bioRxiv2022

Tumor spheroids accelerate persistently invading cancer cells

Glioblastoma brain tumors form in brains white matter and remains one of the most lethal cancers despite intensive therapy and surgery. The complex morphology of these tumors includes infiltrative growth and gain of cell motility. Therefore, various brain-mimetic model systems have been developed to investigate invasion dynamics. Despite this, exactly how gradients of cell density, chemical signals and metabolites influence individual cells migratory behavior remains elusive. Here we show that the gradient field - induced by the spheroid - accelerates cells invasion of the extracellular matrix. We show that cells are pushed away from the spheroid along a radial gradient, as predicted by a biased persistent random walk (BPRW). Thus, our results grasp in a simple model the complex behavior of metastasizing cells. We anticipate that this well-defined and quantitative assay could be instrumental in the development of new anti-cancer strategies.

biophysics↗

bioRxiv2020

Single-cell tracking reveals super-spreading cells with high persistence in invasive brain cancer

Cell migration is a fundamental characteristic of vital processes such as tissue morphogenesis, wound healing and immune cell homing to lymph nodes and inflamed or infected sites. Therefore, various brain defect diseases, chronic inflammatory diseases as well as tumor formation and metastasis are associated with aberrant or absent cell migration. With embedment of multicellular brain cancer spheroids in Matrigel and single-particle tracking, we extracted the paths of cells migrating away from the spheroids. We found that - in contrast to local invasion - single cell migration is independent of the mechanical load exerted by the environment and is characterized by high directionality and persistence. Furthermore, we identified a subpopulation of super-spreading cells with >200-fold longer persistence times than the majority of cells. These results highlight yet another aspect of between-cell heterogeneity in tumors.

biophysics↗