VimAc · Vimentin intermediate filaments: the origin of stretchability and their direct interaction with actin filaments

Vimentin intermediate filaments: the origin of stretchability and their direct interaction with actin filaments

Living cells constantly experience mechanical forces during movement, division, and tissue remodeling. Their ability to withstand and respond to these forces depends on the cytoskeleton, a dynamic network of protein filaments that provides structural support and coordinates cellular functions. The cytoskeleton consists of three major filament types: actin filaments, microtubules, and intermediate filaments (IFs). The organization of and interactions between these filaments are essential for processes such as force transmission, intracellular transport, cell migration, and cell division. While actin filaments and microtubules have been studied extensively, IFs, particularly vimentin IFs, remain less well understood despite their importance in cellular resilience and their involvement in processes such as wound healing and cancer progression. Two key questions motivated this project. First, although actin and vimentin networks frequently cooperate in cells, it remained unclear whether their coupling arises from direct filament–filament interactions or is mediated by protein crosslinkers. Previous studies of reconstituted actin–vimentin networks yielded inconclusive results, leaving the physical basis of actin–vimentin crosstalk unresolved. Second, vimentin IFs are among the most extensible protein filaments known in biology. Their remarkable stretchability has been attributed to structural transitions involving the unfolding of alpha-helical domains into beta-sheet structures during stretching. However, direct structural evidence for these transitions at the single-filament level is still lacking. To address these questions, the project combined reconstituted systems of purified protein filaments with advanced biophysical techniques, including optical tweezers, microfluidics, confocal fluorescence microscopy, atomic force microscopy (AFM), tip-enhanced Raman spectroscopy (TERS), and computer simulation. This reductionist approach enabled direct and quantitative investigation of filament interactions, mechanics, and structure under well-controlled conditions.

Data: CORDIS, © European Union