Focal adhesions are controlled by microtubules through local contractility regulation.

Microtubules regulate cell polarity and migration via local activation of focal adhesion turnover, but the mechanism of this process is insufficiently understood. Molecular complexes containing KANK family proteins connect microtubules with talin, the major component of focal adhesions. Here, local optogenetic activation of KANK1-mediated microtubule/talin linkage promoted microtubule targeting to an individual focal adhesion and subsequent withdrawal, resulting in focal adhesion centripetal sliding and rapid disassembly.

SUN2 regulates mitotic duration in response to extracellular matrix rigidity.

How cells adjust their growth to the spatial and mechanical constraints of their surrounding environment is central to many aspects of biology. Here, we examined how extracellular matrix (ECM) rigidity affects cell division. We found that cells divide more rapidly when cultured on rigid substrates.

Direction of epithelial folding defines impact of mechanical forces on epithelial state.

Cell shape dynamics during development is tightly regulated and coordinated with cell fate determination. Triggered by an interplay between biochemical and mechanical signals, epithelia form complex tissues by undergoing coordinated cell shape changes, but how such spatiotemporal coordination is controlled remains an open question. To dissect biochemical signaling from purely mechanical cues, we developed a microfluidic system that experimentally triggers epithelial folding to recapitulate stereotypic deformations observed in vivo.

Cell fluorescence photoactivation as a method to select and study cellular subpopulations grown in mechanically heterogeneous environments.

A central challenge to the biology of development and disease is deciphering how individual cells process and respond to numerous biochemical and mechanical signals originating from the environment. Recent advances in genomic studies enabled the acquisition of information about population heterogeneity; however, these so far are poorly linked with the spatial heterogeneity of biochemical and mechanical cues. Whereas in vitro models offer superior control over spatiotemporal distribution of numerous mechanical parameters, researchers are limited by the lack of methods to select subpopulations of cells in order to understand how environmental heterogeneity directs the functional collective response.

Nuclear envelope deformation controls cell cycle progression in response to mechanical force.

The shape of the cell nucleus can vary considerably during developmental and pathological processes; however, the impact of nuclear morphology on cell behavior is not known. Here, we observed that the nuclear envelope flattens as cells transit from G1 to S phase and inhibition of myosin II prevents nuclear flattening and impedes progression to S phase. Strikingly, we show that applying compressive force on the nucleus in the absence of myosin II-mediated tension is sufficient to restore G1 to S transition.

Analyzing Mechanotransduction Through the LINC Complex in Isolated Nuclei.

The mechanical properties of the cellular microenvironment can impact many aspects of cell behavior, including molecular processes in the nucleus. Recent studies indicate that the LINC complex and its associated nuclear envelope transmit and transduce mechanical stress into biochemical pathways that ultimately regulate nuclear structure or gene expression. Here we describe a method to apply tensional forces to the LINC complex of isolated nuclei.

Leukocyte RhoA exchange factor Arhgef1 mediates vascular inflammation and atherosclerosis.

Abnormal activity of the renin-angiotensin-aldosterone system plays a causal role in the development of hypertension, atherosclerosis, and associated cardiovascular events such as myocardial infarction, stroke, and heart failure. As both a vasoconstrictor and a proinflammatory mediator, angiotensin II (Ang II) is considered a potential link between hypertension and atherosclerosis. However, a role for Ang II-induced inflammation in atherosclerosis has not been clearly established, and the molecular mechanisms and intracellular signaling pathways involved are not known.

Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads.

Mechanosensitive cell surface adhesion complexes allow cells to sense the mechanical properties of their surroundings. Recent studies have identified both force-sensing molecules at adhesion sites, and force-dependent transcription factors that regulate lineage-specific gene expression and drive phenotypic outputs. However, the signaling networks converting mechanical tension into biochemical pathways have remained elusive.

Mechanotransduction via the nuclear envelope: a distant reflection of the cell surface.

As the largest and stiffest organelle in the cell, the nucleus can be subjected to significant forces generated by the cytoskeleton to adjust its shape and position, and accommodate the cellular machinery during cell migration, differentiation or division. As it was anticipated, recent work showed that mechanosensitive mechanisms exist in the nucleus and regulate its structure and function in response to mechanical force. While the molecular mechanisms that mediate this response are only beginning to be elucidated, the nuclear envelope seems to play a central role in this process.

Under Pressure: Mechanical Stress Management in the Nucleus.

Cells are constantly adjusting to the mechanical properties of their surroundings, operating a complex mechanochemical feedback, which hinges on mechanotransduction mechanisms. Whereas adhesion structures have been shown to play a central role in mechanotransduction, it now emerges that the nucleus may act as a mechanosensitive structure. Here, we review recent advances demonstrating that mechanical stress emanating from the cytoskeleton can activate pathways in the nucleus which eventually impact both its structure and the transcriptional machinery.