Biology subjects

Watson, M. C.

Publications and source records attributed to Watson, M. C..

3 recordsLinked to original sources

bioRxiv2026

A Cone-Plate Bioreactor for Applying Physiologically Derived Shear Stress Waveforms to Study Endothelial Mechanotransduction and Cardiac Cell Signaling

Fluid shear stress is a critical regulator of endothelial cell function and cardiovascular development, yet in vitro platforms often lack the ability to reproduce physiologically relevant, time-dependent flow environments with quantitative precision. Here, we present the design and validation of a macro-scale cone-plate bioreactor engineered to deliver controlled steady and pulsatile shear stress waveforms to endothelial monolayers and engineered tissues. The system integrates a geometry optimized to minimize secondary flow effects, a feedback-controlled motor capable of reproducing complex waveforms, and a viscosity-informed control framework to account for shear-dependent fluid behavior. Using this platform, endothelial cells were exposed to steady and physiologically derived pulsatile shear stresses. Cells exhibited increased alignment and eccentricity under shear, confirming biologically relevant mechanical stimulation. While pulsatile shear did not significantly alter endothelial neuregulin-1 expression, exogenous administration studies revealed a nonlinear, dose-dependent increase in cardiomyocyte proliferation. Furthermore, co-culture experiments demonstrated that shear-conditioned endothelial cells promote cardiomyocyte proliferation, suggesting a mechanotransduction-mediated paracrine signaling mechanism. Together, these results establish a versatile and quantitatively controlled platform for studying cardiovascular mechanobiology. This device enables systematic investigation of shear-dependent cellular responses and provides a foundation for integrating co-culture systems and three-dimensional engineered tissues under physiologically relevant hemodynamic conditions.

bioengineering↗

bioRxiv2026

Non Newtonian Blood Rheology Significantly Alters Hemodynamic Predictions During Cardiac Looping: A Computational Study

Hemodynamic forces play a key role in early cardiac morphogenesis, yet many computational studies assume Newtonian blood behavior. Here, we evaluate the impact of nonNewtonian shearthinning rheology on flow patterns, pressure distributions, and wall shear stress (WSS) during cardiac looping using idealized threedimensional models of the embryonic heart tube. Five geometries representing progressive looping stages, from a linear tube to an Sshaped configuration with ventricular ballooning, were analyzed under pulsatile flow using both Newtonian and powerlaw viscosity models. Across all stages, Reynolds numbers (Re {approx} 1-7) and Womersley numbers (Wo {approx} 0.3) indicated laminar, quasisteady flow consistent with embryonic conditions. Incorporating shearthinning rheology produced substantial deviations from Newtonian predictions, with peak systolic WSS differing by up to [~]40% and pressure drops by up to [~]20%. These effects were most pronounced in regions of increased curvature and geometric complexity. These findings demonstrate that nonNewtonian rheology significantly influences predicted hemodynamic environments during cardiac looping and should be incorporated into computational models aimed at understanding mechanobiological regulation of early heart development.

developmental biology↗

bioRxiv2020

Extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasia

Birth defects, particularly those that affect development of the heart, are a leading cause of morbidity and mortality in infants and young children. Babies born with heart hypoplasia (HH) disorders often have a poor prognosis. It remains unclear whether cardiomyocytes from hypoplastic hearts retain the potential to recover growth, although this knowledge would be beneficial for developing therapies for HH disorders. The objective of this study was to determine the proliferation and maturation potential of cardiomyocytes from hypoplastic hearts and whether these behaviors are influenced by biophysical signaling from the extracellular matrix (ECM) and cyclic mechanical stretch. Congenital diaphragmatic hernia (CDH)-associated HH was induced in rat fetuses by maternal exposure to nitrofen. Hearts were isolated from embryonic day 21 nitrofen-treated fetuses positive for CDH (CDH+) and from fetuses without nitrofen administration during gestation. CDH+ hearts were smaller and had decreased myocardial proliferation, along with evidence of decreased maturity compared to healthy hearts. In culture, CDH+ cardiomyocytes remained immature and demonstrated increased proliferative capacity compared to their healthy counterparts. Culture on ECM derived from CDH+ hearts led to a significant reduction in proliferation for both CDH+ and healthy cardiomyocytes. Healthy cardiomyocytes were dosed with exogenous nitrofen to examine whether nitrofen may have an abhorrent effect on the proliferative ability of cardiomyocyte, yet no significant change in proliferation was observed. When subjected to stretch, CDH+ cardiomyocytes underwent lengthening of sarcomeres while healthy cardiomyocyte sarcomeres were unaffected. Taken together, our results suggest that alterations to environmental cues such as ECM and stretch may be important factors in the pathological progression of HH.

cell biology↗