Response of lymphatic endothelial cells to combined spatial and temporal variations in fluid flow.

One-way valves within lymphatic vessels are required for the efficient drainage of lymphatic fluids. Fluid flow is proposed to be a key cue in regulating both the formation and maintenance of lymphatic valves. However, to our knowledge, no previous study has systematically examined the response of LECs to the complex combination of spatially and temporally varying fluid flows that occur at lymphatic valves in vivo. We built an in vitro microfluidic device that reproduces key aspects of the flow environment found at lymphatic valves. Using this device, we found that a combination of spatially and temporally varying wall shear stresses (WSSs) led to upregulated transcription of PROX1 and FOXC2. In addition, we observed that combined spatial and temporal variations in WSS-modulated Ca2+ signaling and led to increased cellular levels of NFATc1. These observations suggest that the physical cues generated by the flow environment present within lymphatic valves may act to activate key regulatory pathways that contribute to valve maintenance.

Variations in human saliva viscoelasticity affect aerosolization propensity.

Some contagious diseases, such as COVID-19, spread through the transmission of aerosols and droplets. Aerosol and droplet formation occurs inside and outside of the respiratory tract, the latter being observed during speaking and sneezing. Upon sneezing, saliva is expelled as a flat sheet, which destabilizes into filaments that subsequently break up into droplets. The presence of macromolecules (such as mucins) in saliva influences the dynamics of aerosol generation, since elasticity is expected to stabilize both fluid sheets and filaments, hence deterring droplet formation. In this study, the process of aerosol formation outside the respiratory tract is systematically replicated using an impinging jet setup, where two liquid jets collide and form a thin fluid sheet that can fragment into ligaments and droplets. The experimental setup enables us to investigate a range of dynamic conditions, quantified by the relevant non-dimensional numbers, which encompass those experienced during sneezing. Experiments are conducted with human saliva provided by different donors, revealing significant variations in their stability and breakup. We quantify the effect of viscoelasticity via shear and extensional rheology experiments, concluding that the extensional relaxation time is the most adequate measure of a saliva's elasticity. We summarize our results in terms of the dimensionless Weber, Reynolds, and Deborah numbers and construct universal state diagrams that directly compare our data to human sneezing, concluding that the aerosolization propensity is correlated with diminished saliva elasticities, higher emission velocities, and larger ejecta volumes. This could entail variations in disease transmission between individuals which hitherto have not been recognized.