Living cells are constantly exposed to mechanical stimuli arising from the surrounding extracellular matrix (ECM) or from neighboring cells. The intracellular molecular processes through which such physical cues are transformed into a biological response are collectively dubbed as mechanotransduction and are of fundamental importance to help the cell timely adapt to the continuous dynamic modifications of the microenvironment. Local changes in ECM composition and mechanics are driven by a feed forward interplay between the cell and the matrix itself, with the first depositing ECM proteins that in turn will impact on the surrounding cells. As such, these changes occur regularly during tissue development and are a hallmark of the pathologies of aging. Only lately, though, the importance of mechanical cues in controlling cell function (e.g., proliferation, differentiation, migration) has been acknowledged. Here we provide a critical review of the recent insights into the molecular basis of cellular mechanotransduction, by analyzing how mechanical stimuli get transformed into a given biological response through the activation of a peculiar genetic program. Specifically, by recapitulating the processes involved in the interpretation of ECM remodeling by Focal Adhesions at cell-matrix interphase, we revise the role of cytoskeleton tension as the second messenger of the mechanotransduction process and the action of mechano-responsive shuttling proteins converging on stage and cell-specific transcription factors. Finally, we give few paradigmatic examples highlighting the emerging role of malfunctions in cell mechanosensing apparatus in the onset and progression of pathologies.

Hippo effectors YAP/TAZ act as on–off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described by a hierarchical model in which elements of Hippo pathway are under the control of focal adhesions (FAs). Here we unveil the molecular mechanism by which cell spreading and RhoA GTPase activity control FA formation through YAP to stabilize the anchorage of the actin cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional function and involves the activation of genes encoding for integrins and FA docking proteins. Tuning YAP transcriptional activity leads to the modification of cell mechanics, force development and adhesion strength, and determines cell shape, migration and differentiation. These results provide new insights into the mechanism of YAP mechanosensing activity and qualify this Hippo effector as the key determinant of cell mechanics in response to ECM cues.

BackgroundDuring the COVID-19 pandemic, the use of protection masks is essential to reduce contagions. However, public opinion reports an associated subjective shortness of breath. We evaluated cardiorespiratory parameters at rest and during maximal exertion to highlight any differences with the use of protection masks.MethodsTwelve healthy subjects underwent three cardiopulmonary exercise tests: without wearing protection mask, with surgical and with FFP2 mask. Dyspnea was assessed by Borg Scale. Standard pulmonary function tests were also performed.ResultsAll the subjects (40.8±12.4 years; 6 males) completed the protocol with no adverse event. At spirometry, from no mask to surgical to FFP2, a progressive reduction of FEV1 and FVC was observed (3.94±0.91 l, 3.23±0.81 l, 2.94±0.98 l and 4.70±1.21 l, 3.77±1.02 l, 3.52±1.21 l, respectively, p<0.001). Rest ventilation, O2 uptake (V̇O2) and CO2 production (VCO2) were progressively lower with a reduction of respiratory rate. At peak exercise, subjects revealed a progressively higher Borg scale when wearing surgical and FFP2. Accordingly, at peak exercise, V̇O2 (31.0±23.4, 27.5±6.9, 28.2±8.8 ml/kg/min, p=0.001), ventilation (92±26, 76±22, 72±21 l, p=0.003), respiratory rate (42±8, 38±5, 37±4, p=0.04) and tidal volume (2.28±0.72, 2.05±0.60, 1.96±0.65 l, p=0.001) were gradually lower. We did not observed a significant difference in oxygen saturation.ConclusionsProtection masks are associated with significant but modest worsening of spirometry and cardiorespiratory parameters at rest and peak exercise. The effect is driven by a ventilation reduction due to an increased airflow resistance. However, since exercise ventilatory limitation is far from being reached, their use is safe even during maximal exercise, with a slight reduction in performance.

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