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Phung, T.-K. N.

Publications and source records attributed to Phung, T.-K. N..

2 recordsLinked to original sources

In airway epithelium, basal stem cells and their stress fibers remodel during the unjamming transition

Under homeostatic conditions, epithelial cells remain non-migratory. However, during embryonic developmental and pathological processes, they become migratory. The mechanism underlying the transition between non-migratory and migratory epithelial cells is a fundamental question of cellular biology. In well-differentiated primary human bronchial epithelial cell layers, non-migratory epithelial cells become migratory through an unjamming transition (UJT). We have previously identified the hallmarks of UJT: apical cell elongation and collective cellular migration. These indicate that UJT is driven by intercellular force modulation, but the nature of these forces in pseudostratified epithelia is unknown. Here, we identify structural characteristics of basal stem cells that are indicative of force generation. During the UJT, basal stem cells elongate and enlarge, and their stress fibers lengthen and align. These morphological changes in basal stem cells correspond to the previously defined hallmarks of the UJT. Moreover, basal cell elongation and stress fiber lengthening precedes apical cell elongation. Together, these structural changes in basal stem cells suggest that in pseudostratified airway epithelium, basal stem cells may be the origin of the traction forces through stress fiber modeling during the UJT. Summary StatementOur image analysis of pseudostratified airway epithelium reveals basal stem cells as the likely source of traction forces driving collective cellular migration during an unjamming transition.

cell biology↗

A Rapid Electromechanical Model To Predict Reverse Remodeling Following Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) is an ef-fective therapy for patients who suffer from heart failure and ventricular dyssynchrony such as left bundle branch block (LBBB). When it works, it reverses adverse left ventricular (LV) remodeling and the progression of heart failure. How-ever, CRT response rate is currently as low as 50-65%. In theory, CRT outcome could be improved by allowing clinicians to tailor the therapy through patient-specific lead locations, timing, and/or pacing protocol. However, this also presents a dilemma: there are far too many possible strategies to test during the implantation surgery. Computational models could address this dilemma by predicting remodeling outcomes for each patient before the surgery takes place. Therefore, the goal of this study was to develop a rapid computational model to predict reverse LV remodeling following CRT. We adapted our recently developed computational model of LV remodeling to simulate the mechanics of ventricular dyssynchrony and added a rapid electrical model to predict electrical activation timing. The model was calibrated to quantitatively match changes in hemodynamics and global and local LV wall mass from a canine study of LBBB and CRT. The calibrated model was used to investigate the influence of LV lead location and ischemia on CRT remodeling outcome. Our model results suggest that remodeling outcome varies with both lead location and ischemia location, and does not always correlate with short-term improvement in QRS duration. The results and time frame required to customize and run this model suggest promise for this approach in a clinical setting.

bioengineering↗