Search

Detection and conversion of mechanical forces into biochemical signals is known as mechanotransduction. From cells to tissues, mechanotransduction regulates migration, proliferation, and differentiation in processes such as immune responses, development, and cancer progression. Mechanosensitive structures such as integrin adhesions, the actin cortex, ion channels, caveolae, and the nucleus sense and transmit forces. In vitro approaches showed that mechanosensing is based on force-dependent protein deformations and reorganizations. However, the mechanisms in cells remained unclear since cell imaging techniques lacked molecular resolution. Thanks to recent developments in super-resolution microscopy (SRM) and molecular force sensors, it is possible to obtain molecular insight of mechanosensing in live cells. We discuss how understanding of molecular mechanotransduction was revolutionized by these innovative approaches, focusing on integrin adhesions, actin structures, and the plasma membrane. Mechanotransduction is involved in a variety of cell and tissue processes. For this, mechanosensitive structures, such as integrin adhesions, the cytoskeleton, or the plasma membrane, are key to sense, integrate, and transmit mechanical forces. Novel imaging methods and molecular sensors have unveiled how molecular mechanosensing occurs in these structures within the context of live cells. These include super-resolution imaging, single particle tracking, and molecular force sensors. Super-resolution microscopy and single protein tracking have revealed the 3D nanoscale organization and dynamics of integrin adhesion structures in various cell types, which are divided into functional nanolayers with specific paths for protein diffusion. Forces on actin regulators and F-actin trigger conformational changes controlling actin regulator function and binding, and therefore F-actin assembly and architecture. In migrating cells, mechanical plasticity emerges from global geometrical reorganization of actin networks under loads, or forces from elongating actin filaments controlling locally actin regulators dynamics and functions. Cell surface mechanics are emerging as a key parameter controlling cell motility, division, and differentiation. Variations in cortical tension and membrane-to-cortex attachment regulate the timing of differentiation while the nanoscale architecture of the actin cortex is linked to cortical tension. [ABSTRACT FROM AUTHOR]

Intermediate filaments (IFs) are involved in key cellular functions including polarization, migration, and protection against large deformations. These functions are related to their remarkable ability to extend without breaking, a capacity that should be determined by the molecular organization of subunits within filaments. However, this structure-mechanics relationship remains poorly understood at the molecular level. Here, using super-resolution microscopy (SRM), we show that vimentin filaments exhibit a ~49-nanometer axial repeat both in cells and in vitro. As unit-length filaments (ULFs) were measured at ~59 nanometers, this demonstrates a partial overlap of ULFs during filament assembly. Using an SRM-compatible stretching device, we also provide evidence that the extensibility of vimentin is due to the unfolding of its subunits and not to their sliding, thus establishing a direct link between the structural organization and its mechanical properties. Overall, our results pave the way for future studies of IF assembly, mechanical, and structural properties in cells.