Biology subjects

Nagle, I.

Publications and source records attributed to Nagle, I..

3 recordsLinked to original sources

bioRxiv2025

Invasive cancer cells soften collagen networks and disrupt stress-stiffening via volume exclusion, contractility and adhesion

Collagen networks form the structural backbone of the extracellular matrix in both healthy and cancerous tissues, exhibiting nonlinear mechanical properties that crucially regulate tissue mechanics and cell behavior. Here, we investigate how the presence of invasive breast cancer cells (MDA-MB-231) influences the polymerization kinetics and mechanics of collagen networks using bulk shear rheology and rheo-confocal microscopy. We show that embedded cancer cells delay the onset of collagen polymerization due to volume exclusion effects. During polymerization, the cells (at 4% volume fraction) cause an unexpected time-dependent softening of the network. We show that this softening effect arises from active remodeling via adhesion and contractility rather than from proteolytic degradation. At higher cell volume fractions, the dominant effect of the cells shifts to volume exclusion, causing a two-fold reduction of network stiffness. Additionally, we demonstrate that cancer cells suppress the characteristic stress-stiffening response of collagen. This effect (partially) disappears when cell adhesion and contractility are inhibited, and it is absent when the cells are replaced by passive hydrogel particles. These findings provide new insights into how active inclusions modify the mechanics of fibrous networks, contributing to a better understanding of the role of cells in the mechanics of healthy and diseased tissues like invasive tumors.

biophysics↗

bioRxiv2024

Mechanical constraints organize 3D tissues and orchestrate muscle differentiation

Biological tissues achieve proper shape and ordered structures during development through responses to internal and external signals, with mechanical cues playing a crucial role. These forces guide cellular organization, leading to complex self-organizing structures that are foundational to embryonic patterns. Emerging theories and experiments suggest that "topological morphogens" drive these processes. Despite the predominance of three-dimensional (3D) structures in biology, studying 3D tissues remains challenging due to limited model systems and the complexity of modeling. Here, we address these challenges by using self-organized cellular aggregates, specifically spindle-shaped C2C12 myoblasts, subjected to controlled mechanical stretching. Our findings reveal that these cells form a multilayered, actin-oriented tissue structure, where mechanical forces drive long-range 3D organization and muscle differentiation. Notably, tissue surface emerges as a hotspot for differentiation, correlating with directional order as shown by single molecule fluorescent in situ hybridization. Significance StatementWe explore how cells work together to form complex structures, particularly in 3D, using muscle precursors cells (C2C12 myoblasts) as a model. By applying controlled stretching forces, we found that these cells self-organize into layered tissues that guide their transformation into muscle. This research highlights the critical role of physical forces in shaping tissues, suggesting that the way cells are physically arranged and stretched in three dimensions can significantly influence their behavior and function. Our findings offer new insights into how tissues develop and could have implications for tissue engineering, where creating the right 3D environment is key to successful tissue growth and repair.

biophysics↗

bioRxiv2021

Multiparameters dependance of tissue shape maintenance in myoblasts multicellular aggregates: the role of intermediate filaments.

Liquid and elastic behavior of tissues drives their morphology and their response to the environment. They appear as the first insight on tissue mechanics. We explore the role of individual cell properties on spheroids of mouse muscle precursor cells by developing a fully automated surface tension and Youngs modulus measurement system. Flattening multicellular aggregates under magnetic constraint, we show that rigidity and surface tension act as highly sensitive macroscopic reporters closely related to microscopic local tension and effective adhesion. Shedding light on the major contributions of acto-myosin contractility, actin organization and intercellular adhesions, we reveal the role of desmin organization on the macroscopic mechanics of this tissue model.

biophysics↗