Biology subjects

Janssen, L. M. C.

Publications and source records attributed to Janssen, L. M. C..

2 recordsLinked to original sources

bioRxiv2025

Disentangling the interplay between cell-cell and cell-matrix interactions in cancer cell migration

Metastasis proceeds through the dissemination of cells from the primary tumor into the surrounding extracellular matrix (ECM), initiating further spread throughout the body. The invasion of cancer cells into the ECM is significantly influenced by cell-cell adhesion, cell-matrix adhesion, and the generation of traction forces. However, the complex interplay between these different aspects makes it difficult to disentangle their roles in the invasive process, hampering our mechanistic understanding of collective cell invasion. Here, we combine integrin knockout experiments in Hs578T and 4T1 breast cancer cell lines with a computational cellular Potts model to elucidate the biophysical mechanisms underlying invasive cell behavior. By tuning the cell-cell and cell-matrix adhesion parameters in our computational model, we establish a quantitative mapping with the experiments. Our work reveals that strong cell-matrix interactions promote invasion, while strong cell-cell adhesion promotes the formation and dissemination of multicellular clusters. Moreover, our model delineates a threshold for invasion and predicts that tumor morphology - particularly the number of branches from the primary tumor - correlates with its invasive potential, suggesting that morphological tumor features may serve as a proxy for metastasis. Our approach highlights the importance of combining biological experiments with computational and predictive modeling, offering new insights into the mechanisms driving cancer cell migration.

biophysics↗

bioRxiv2020

Characterising the Diffusion of Biological Nanoparticles on Fluid and Elastic Membranes

Tracing the motion of macromolecules, viruses, and nanoparticles adsorbed onto cell membranes is currently the most direct way of probing the complex dynamic interactions behind vital biological processes, including cell signalling, trafficking, and viral infection. The resulting trajectories are usually consistent with some type of anomalous diffusion, but the molecular origins behind the observed anomalous behaviour are usually not obvious. Here we use coarse-grained molecular dynamics simulations to help identify the physical mechanisms that can give rise to experimentally observed trajectories of nanoscopic objects moving on biological membranes. We find that diffusion on membranes of high fluidities typically results in normal diffusion of the adsorbed nanoparticle, irrespective of the concentration of receptors, receptor clustering, or multivalent interactions between the particle and membrane receptors. Gel-like membranes on the other hand result in anomalous diffusion of the particle, which becomes more pronounced at higher receptor concentrations. This anomalous diffusion is characterised by local particle trapping in the regions of high receptor concentrations and fast hopping between such regions. The normal diffusion is recovered in the limit where the gel membrane is saturated with receptors. We conclude that hindered receptor diffusivity can be a common reason behind the observed anomalous diffusion of viruses, vesicles, and nanoparticles adsorbed on cell and model membranes. Our results enable direct comparison with experiments and offer a new route for interpreting motility experiments on cell membranes.

biophysics↗