Publications

The directed migration of cellular clusters enables morphogenesis, wound healing and collective cancer invasion. Gradients of substrate stiffness direct the migration of cellular clusters in a process called collective durotaxis, but the underlying mechanisms remain unclear. Here we unveil a connection between collective durotaxis and the wetting properties of cellular clusters. We show that clusters of cancer cells dewet soft substrates and wet stiff ones. At intermediate stiffness-at the crossover from low to high wettability-clusters on uniform-stiffness substrates become maximally motile, and clusters on stiffness gradients exhibit optimal durotaxis. Durotactic velocity increases with cluster size, stiffness gradient and actomyosin activity. We demonstrate this behaviour on substrates coated with the cell-cell adhesion protein E-cadherin and then establish its generality on substrates coated with extracellular matrix. We develop an active wetting model that explains collective durotaxis in terms of a balance between in-plane active traction and tissue contractility and out-of-plane surface tension. Finally, we show that the distribution of cluster displacements has a heavy tail, with infrequent but large cellular hops that contribute to durotactic migration. Our study demonstrates a physical mechanism of collective durotaxis, through both cell-cell and cell-substrate adhesion ligands, based on the wetting properties of active droplets.

JTD Keywords: Adhesion, Dynamics, E-cadherin, Gradient, Migration, Model, Motility, Movements, Rigidity, Substrate stiffness

Patients suffering from obstructive sleep apnea (OSA) usually present an increased sympathetic activity caused by the intermittent hypoxia effect on autonomic control. This study evaluated the relationship between sleep stages and the apnea duration, frequency, and type, as well as their impact on HRV markers in different groups of disease severity. The hypnogram and R-R interval signals were extracted in 81 OSA patients from night polysomnographic (PSG) recordings. The apnea-hypopnea index (AHI) defined patient classification as mild-moderate (AHI< 30, n 44) or severe (AHI>30, n 37). The normalized power in VLH, LF, and HF bands of RR series were estimated by a time-frequency approach and averaged in 1-min epochs of normal and apnea segments. The autonomic response and the impact of sleep stages were assessed in both segments to compare patient groups. Deeper sleep stages (particularly S2) concentrated the shorter and mild apnea episodes (from 10 to 40 s) compared to light (SWS) and REM sleep. Longer episodes (>50 s) although less frequent, were of similar incidence in all stages. This pattern was more pronounced for the group of severe patients. Moreover, during apnea segments, LF nu was higher (p 0.044) for the severe group, since V LF nu and HF nu presented the greatest changes when compared to normal segments. The non-REM sleep seems to better differentiate OSA patients groups, particularly through VLF nu and HF nu (p<0.001). A significant difference in both sympathetic and vagal modulation between REM and non-REM sleep was only found within the severe group. These results confirm the importance of considering sleep stages for HRV analysis to further assess OSA disease severity, beyond the traditional and clinically limited AHI values.Clinical relevance - Accounting for sleep stages during HRV analysis could better assess disease severity in OSA patients. © 2021 IEEE.

JTD Keywords: blood-pressure, genomic consequences, intermittent hypoxia, rapid-eye-movement, sympathetic activity, Heart rate, Heart-rate-variability, Human, Humans, Polysomnography, Rem sleep, Sleep apnea, obstructive, Sleep disordered breathing, Sleep stage, Sleep stages, Sleep, rem

Objective. Impaired trunk stability is frequent in spinal cord injury (SCI), but there is a lack of quantitative measures for assessing trunk function. Our objectives were to: (a) evaluate trunk muscle activity and movement patterns during a reaching task in SCI patients, (b) compare the impact of cervical (cSCI) and thoracic (tSCI) injuries in trunk function, and (c) investigate the effects of a startling acoustic stimulus (SAS) in these patients. Approach. Electromyographic (EMG) and smartphone accelerometer data were recorded from 15 cSCI patients, nine tSCI patients, and 24 healthy controls, during a reaching task requiring trunk tilting. We calculated the response time (RespT) until pressing a target button, EMG onset latencies and amplitudes, and trunk tilt, lateral deviation, and other movement features from accelerometry. Statistical analysis was applied to analyze the effects of group (cSCI, tSCI, control) and condition (SAS, non-SAS) in each outcome measure. Main results. SCI patients, especially those with cSCI, presented significantly longer RespT and EMG onset latencies than controls. Moreover, in SCI patients, forward trunk tilt was accompanied by significant lateral deviation. RespT and EMG latencies were remarkably shortened by the SAS (the so-called StartReact effect) in tSCI patients and controls, but not in cSCI patients, who also showed higher variability. Significance. The combination of EMG and smartphone accelerometer data can provide quantitative measures for the assessment of trunk function in SCI. Our results show deficits in postural control and compensatory strategies employed by SCI patients, including delayed responses and higher lateral deviations, possibly to improve sitting balance. This is the first study investigating the StartReact responses in trunk muscles in SCI patients and shows that the SAS significantly accelerates RespT in tSCI, but not in cSCI, suggesting an increased cortical control exerted by these patients.

JTD Keywords: accelerometer, electromyography, impairment, individuals, movements, postural stability, reaction-time, reliability, sitting balance, smartphone, spinal cord injury, startle, startreact, strategies, stroke, trunk, Accelerometer, Electromyography, Sitting balance, Smartphone, Spinal cord injury, Startreact, Trunk

Novel hybrid, fibrinogen/polylactic acid (FBG/PLA) nanofibers with different configuration (random vs. aligned) and dimensionality (2D vs.3D environment) were used to control the overall behaviour and the osteogenic differentiation of human Adipose Derived Mesenchymal Stem Cells (ADMSCs). Aligned nanofibers in both the 2D and 3D configurations are proved to be favoured for osteo-differentiation. Morphologically we found that on randomly configured nanofibers, the cells developed a stellate-like morphology with multiple projections, however, time-lapse analysis showed significantly diminished cell movements. Conversely, an elongated cell shape with advanced cell spreading and extended actin cytoskeleton accompanied with significantly increased cell mobility were observed when cells attached on aligned nanofibers. Moreover, a clear tendency for higher alkaline phosphatase activity was also found on aligned fibres when ADMSCs were switched to osteogenic induction medium. The strongest accumulation of Alizarin red (AR) and von Kossa stain at 21 day of culture in osteogenic medium were found on 3D aligned constructs while the rest showed lower and rather undistinguishable activity. Quantitative reverse transcription-polymerase chain reaction analysis for Osteopontin (OSP) and RUNX 2 generally confirmed this trend showing favourable expression of osteogenic genes activity in 3D environment particularly in aligned configuration.

JTD Keywords: Mesenchymal stem cells, Nanofibers, Osteogenic, Fibrinogen, Cell movements

This paper presents a study on how the application of scaling techniques to an interface affects its performance. A progressive scaling factor based on the position and velocity of the cursor and the targets improves the efficiency of an interface, thereby reducing the user's workload. The study uses several human-motor models to interpret human intention and thus contribute to defining and adapting the scaling parameters to the execution of the task. Two techniques addressed to vary the control-display ratio are compared, and a new method for aiding in the task of steering is proposed.

JTD Keywords: Performance, Movements