Biology subjects

van der Net, A.

Publications and source records attributed to van der Net, A..

3 recordsLinked to original sources

bioRxiv2025

Cancer cell deformability impacts the rate of confined migration but not decision making

Cancer cells can utilize different invasion strategies to overcome physical arrest during confined migration through tissues with small pores. Cancer cell plasticity allows switches between different migration modes and transitions between single-cell and collective migration. The biophysical parameters that guide these decisions are poorly understood. In this work we investigated the link between cell deformability and migration efficacy in constrictions of two mesenchymal cancer cell types with similar invasion strategies: HT1080 fibrosarcoma cells and MV3 melanoma cells. To this end, we designed microfluidic platforms for (1) high-throughput cell deformability measurements and (2) migration through a variety of confining geometries. We measured different deformabilities for HT1080 and MV3 cells and correlated this to their migration efficacy through confinements. However, higher deformability and improved squeezing ability did not impact decision-making at junctions of channels of different widths. Our findings show that cell deformability correlates with better squeezing abilities through confinements, but does not impact directionality decisions.

cancer biology↗

bioRxiv2024

EMT-dependent cell-matrix interactions are linked to unjamming transitions in cancer spheroid invasion

The plasticity of cancer cells allows them to switch between different migration modes, promoting their invasion into the extracellular matrix (ECM) and hence increasing the risks of metastasis. Epithelial-to-mesenchymal transitions (EMT) and unjamming transitions provide two distinct pathways for cancer cells to become invasive, but it is still unclear to what extent these pathways are connected. Here we addressed this question by performing 3D spheroid invasion assays of lung adenocarcinoma (A549, epithelial) and melanoma (MV3, mesenchymal-like) cancer cell lines in collagen-based hydrogels, where we varied both the invasive character of the cells (using Transforming Growth Factor (TGF)-{beta} to promote EMT and matrix metalloprotease (MMP) inhibition to block cell-mediated matrix degradation) and the porosity of the matrix. Using a quantitative image analysis method to track spheroid invasion, we discovered that the onset time of invasion mostly depended on the matrix porosity and corresponded with vimentin levels, while the subsequent spheroid expansion rate mostly depended on metalloprotease MMP1 levels and thus cell-matrix interaction. Morphological analysis revealed that spheroids displayed solid-like (non-invasive) behavior in small-pore hydrogels and switched to fluid-like (strand-based) or gas-like (disseminating cells) phases in large-pore hydrogels and when cells were more mesenchymal-like. Our findings are consistent with unjamming transitions as a function of cell motility and matrix confinement predicted in recent models for cancer invasion, but show that cell motility and matrix confinement are coupled via EMT-dependent matrix degradation.

cancer biology↗

bioRxiv2023

Elucidating the role of water in collagen self assembly by isotopically modulating collagen hydration

Water is known to play an important role in collagen self assembly, but it is still largely unclear how water-collagen interactions influence the assembly process and determine the fibril network properties. Here, we use the H2O/D2O isotope effect on the hydrogen-bond strength in water to investigate the role of hydration in collagen self assembly. We dissolve collagen in H2O and D2O, and compare the growth kinetics and the structure of the collagen assemblies formed in these water isotopomers. Surprisingly, collagen assembly occurs ten times faster in D2O than in H2O, and collagen in D2O self assembles into much thinner fibrils, that form a more inhomogeneous and softer network, with a fourfold reduction in elastic modulus compared to H2O. Combining spectroscopic measurements with atomistic simulations, we show that collagen in D2O is less hydrated than in H2O. This partial dehydration lowers the enthalpic penalty for water removal and reorganization at the collagen-water interface, increasing the self assembly rate and the number of nucleation centers, leading to thinner fibrils and a softer network. Coarse-grained simulations show that the acceleration in the initial nucleation rate can be reproduced by the enhancement of electrostatic interactions, which appear to be crucial in determining the acceleration of the initial nucleation rate. These results show that water acts as a mediator between collagen monomers, by moderating their interactions so as to optimize the assembly process and, thus, the final network properties. We believe that isotopically modulating the hydration of proteins can be a valuable method to investigate the role of water in protein structural dynamics and protein self assembly.

biophysics↗