Researchers have uncovered new mechanisms by which cells adhere to and spread across fluid membranes, demonstrating the complex role of microtubules. This finding is significant, as it challenges previous beliefs about the limitations of integrin-mediated adhesion on flexible substrates.
The study focused on supported lipid bilayers (SLBs) coated with Yersinia bacterial protein known as invasins, which serve as high-affinity integrin ligands. Unlike traditional methods using rigid substrates, the researchers discovered cells could form larger and more complex integrin clusters on these fluid membranes.
Traditional views suggested integrin-ligand complexes on such surfaces could not effectively anchor, thereby preventing cell spreading. The new data reveals just the opposite: cells demonstrate significant spreading, comparable to those on glass. This was evidenced by detailed quantitative measurements of the growing integrin clusters during cell adhesion.
Using advanced imaging techniques, the team quantified β1-integrin clustering on both RGD and invasins weathered surfaces. They found notable differences: integrin clusters on invasins-SLBs were not only larger but also denser than their counterparts on RGD peptides under similar conditions. This was presumably due to qualitatively different receptor-ligand affinities, which also facilitated mechanotransduction pathways.
One of the study's significant discoveries is the mechanical action of microtubules on integrin clusters. The team determined through careful observation and modeling how vertical forces exerted on these clusters impact cell adhesion and spreading. The inhibition of microtubule activity resulted in diminished integrin density, showing how these structures facilitate connectivity necessary for adhesion on fluid membranes.
Surprisingly, cells on these low-viscosity invasins-SLBs formed protrusions symmetrically without directional polarization. The presence of such protrusions correlated with enhanced integrin clustering and spreading, which was distinctly different from behaviors of cells on RGD-SLBs. This suggests there are underlying mechanical processes at work impacting how cells interact with fluid surfaces.
Theoretical models have been proposed to explain these mechanisms, indicating the potential for vertical force components generated by microtubule dynamics to induce conformational changes necessary for integrin clustering. Importantly, these findings speak to broader biological processes, including how immune cells interact during responses to pathogens.
Integrin clusters migrate to the cell periphery with the help of forces applied by dynein motors, which underline the complex interplay between different cellular components during adhesion on fluid surfaces. This study positions microtubules as key players not just for structural support, but also for the dynamic behavior of cells as they spread across flexible membranes.
Overall, the work advances our knowledge of cellular mechanics on fluid substrates, with potential applications extending to tissue engineering and regenerative medicine, where cell behavior on soft matrices is pivotal.