Biology subjects

Kimps, L.

Publications and source records attributed to Kimps, L..

3 recordsLinked to original sources

bioRxiv2025

Data-driven traction force microscopy in 3D collagen hydrogels

Quantitative measurements of cell-generated forces in fibrillar hydrogels have traditionally modeled the extracellular matrix as a continuum. Here we present a data-driven 3D traction force microscopy (DD-TFM) approach that reconstructs discrete collagen fiber networks from second-harmonic generation images and assigns fiber mechanics calibrated by shear rheology. In silico tests confirm the robustness of an inverse force-recovery method, and application to cells in collagen reveals pulling patterns and fiber-level stress distributions.

biophysics↗

bioRxiv2025

Osteoarthritis leads to more contractile and protrusive chondrocytes when cultured in 3D degradable hydrogels

Osteoarthritis (OA) induces phenotypic changes in chondrocytes as well as alterations in matrix composition and mechanics. Yet, its impact on active cell-generated forces, a key indicator of cell-matrix interaction, remains poorly characterized. In this study, we systematically compared the force generation capacity and associated proteins of interest between human OA and non-OA articular chondrocytes and how they are affected by cell culture dimensionality (2D versus 3D) and matrix degradability. Using traction force microscopy (TFM) combined with high-resolution immunostainings we show that OA alters the expression and organization of proteins involved in force exertion and transmission across both 2D and 3D cultures, but only in a 3D degradable hydrogel environment do these changes translate into higher cell-generated contractile forces This increased force generation correlates with elevated protrusive activity, higher actomyosin content and engagement, as well as altered localization of adhesion and matrix proteins, all of which could contribute to increased cell-matrix interaction in OA chondrocytes. In contrast, OA chondrocytes display no increase in cell tractions when cultured on 2D hydrogel substrates. These findings demonstrate that the detection and interpretation of OA-related alterations in chondrocyte mechanobiology are strongly dependent on the dimensionality and degradable properties of the culture system. Our results highlight the critical role of 3D degradable environments in revealing disease-associated changes in chondrocyte force generation and emphasize the necessity of carefully selecting model systems when investigating OA mechanobiology.

bioengineering↗

bioRxiv2025

Linking Molecular Tension and Cellular Tractions: A Multiscale Approach to Focal Adhesion Mechanics

Focal adhesions (FAs) are mechanosensitive structures that mediate force transmission between cells and the extracellular matrix. While Traction Force Microscopy (TFM) quantifies cellular tractions exerted on deformable substrates, Forster Resonance Energy Transfer (FRET)-based tension probes, such as Vinculin Tension Sensors (VinTS), measure molecular-scale forces within FA proteins. Despite their potential synergy, these methods have rarely been combined to explore the interplay between molecular tension and cellular tractions. Here, we introduce a framework integrating TFM and VinTS to investigate FA mechanics across scales. At cell level, tractions and vinculin tension increased with substrate stiffness. At FA level, vinculin tension correlated with vinculin density, while tractions scaled with FA area, total vinculin content and vinculin density. Direct comparison of tractions to tension revealed a complex, heterogenous relationship between these forces, possibly linked to diverse cell and FA maturation states. Sub-FA analysis revealed conserved spatial patterns, with tension and traction increasing towards the cell periphery. This multiscale approach provides insights into the multiscale dynamics of FA mechanotransduction, bridging the gap between molecular forces and cellular mechanics.j

biophysics↗