Mechanosensitive FHL2 tunes endothelial function.

Endothelial tissues are essential mechanosensors in the vasculature and facilitate adaptation to various blood flow-induced mechanical cues. Defects in endothelial mechanoresponses can perturb tissue remodelling and functions leading to cardiovascular disease progression. In this context, the precise mechanisms of endothelial mechanoresponses contributing to normal and diseased tissue functioning remain elusive.

Machine learning interpretable models of cell mechanics from protein images.

Cellular form and function emerge from complex mechanochemical systems within the cytoplasm. Currently, no systematic strategy exists to infer large-scale physical properties of a cell from its molecular components. This is an obstacle to understanding processes such as cell adhesion and migration.

Zyxin is all you need: machine learning adherent cell mechanics.

Cellular form and function emerge from complex mechanochemical systems within the cytoplasm. No systematic strategy currently exists to infer large-scale physical properties of a cell from its many molecular components. This is a significant obstacle to understanding biophysical processes such as cell adhesion and migration.

Quantifying Strain-Sensing Protein Recruitment During Stress Fiber Repair.

A family of proteins have been identified that recognize damaged, strained actin filaments in stress fibers. These proteins are often referred to as strain- or force-sensing and trigger downstream signaling mechanisms that can facilitate repair at these strain sites. Here we describe a method using high-resolution microscopy to screen and quantify the mechanosensitive recruitment of proteins to these stress fiber strain sites.

Non-catalytic allostery in α-TAT1 by a phospho-switch drives dynamic microtubule acetylation.

Spatiotemporally dynamic microtubule acetylation underlies diverse physiological and pathological events. Despite its ubiquity, the molecular mechanisms that regulate the sole microtubule acetylating agent, α-tubulin-N-acetyltransferase-1 (α-TAT1), remain obscure. Here, we report that dynamic intracellular localization of α-TAT1 along with its catalytic activity determines efficiency of microtubule acetylation.

Microtubules tune mechanosensitive cell responses.

Mechanotransduction is a process by which cells sense the mechanical properties of their surrounding environment and adapt accordingly to perform cellular functions such as adhesion, migration and differentiation. Integrin-mediated focal adhesions are major sites of mechanotransduction and their connection with the actomyosin network is crucial for mechanosensing as well as for the generation and transmission of forces onto the substrate. Despite having emerged as major regulators of cell adhesion and migration, the contribution of microtubules to mechanotransduction still remains elusive.

Cytoskeletal Crosstalk in Cell Migration.

Cell migration is a highly dynamic process driven by the cytoskeleton, which mainly comprises the actin microfilaments, microtubules, and intermediate filaments. During migration, cells polarize and form protrusions at the front, where new adhesions are formed. These nascent adhesions mature into focal adhesions that transmit the traction forces required for movement.

Microtubules at focal adhesions - a double-edged sword.

Cell adhesion to the extracellular matrix is essential for cellular processes, such as migration and invasion. In response to cues from the microenvironment, integrin-mediated adhesions alter cellular behaviour through cytoskeletal rearrangements. The tight association of the actin cytoskeleton with adhesive structures has been extensively studied, whereas the microtubule network in this context has gathered far less attention.

Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and astrocyte migration.

Microtubules play a crucial role in mesenchymal migration by controlling cell polarity and the turnover of cell adhesive structures on the extracellular matrix. The polarized functions of microtubules imply that microtubules are locally regulated. Here, we investigated the regulation and role of two major tubulin post-translational modifications, acetylation and detyrosination, which have been associated with stable microtubules.

Intermediate filaments control collective migration by restricting traction forces and sustaining cell-cell contacts.

Mesenchymal cell migration relies on the coordinated regulation of the actin and microtubule networks that participate in polarized cell protrusion, adhesion, and contraction. During collective migration, most of the traction forces are generated by the acto-myosin network linked to focal adhesions at the front of leader cells, which transmit these pulling forces to the followers. Here, using an in vitro wound healing assay to induce polarization and collective directed migration of primary astrocytes, we show that the intermediate filament (IF) network composed of vimentin, glial fibrillary acidic protein, and nestin contributes to directed collective movement by controlling the distribution of forces in the migrating cell monolayer.

Integrin diversity brings specificity in mechanotransduction.

Cells sense and respond to the biochemical and physical properties of the extracellular matrix (ECM) through adhesive structures that bridge the cell cytoskeleton and the surrounding environment. Integrin-mediated adhesions interact with specific ECM proteins and sense the rigidity of the substrate to trigger signalling pathways that, in turn, regulate cellular processes such as adhesion, motility, proliferation and differentiation. This process, called mechanotransduction, influenced by the involvement of different integrin subtypes and their high ECM-ligand binding specificity, contributes to the cell-type-specific mechanical responses.

The RNA-binding protein LARP4 regulates cancer cell migration and invasion.

LARP4 is a La-related RNA-binding protein implicated in regulating mRNA translation, which interacts with poly(A)-binding protein (PABP). We previously identified LARP4 in an RNAi screen as one of several genes that regulate the shape of PC3 prostate cancer cells. Here we show that LARP4 depletion induces cell elongation in PC3 cells and MDA-MB-231 breast cancer cells.