Poster Presentation: Benjamin Goykadosh

ABSTRACT

A Self-Sustaining Mechanism for Endothelial Tension Maintenance Through GqGPCR Signaling

Benjamin M. Goykadosh1, Vasuretha Chandar1, and Harikrishnan Parameswaran1

Dept. of Bioengineering, Northeastern University, Boston, MA

The vascular endothelium maintains vascular homeostasis through its ability to generate and sustain mechanical tension, allowing the passage of nutrients, immune cells, and signaling molecules while serving as a barrier to pathogens. Aging and disease alter the vascular environment and disrupt the regulation of endothelial tension, contributing to vascular diseases such as hypertension and atherosclerosis. Although endothelial mechanics are known to be influenced by changes in the cellular environment, the mechanisms that enable endothelial cells (ECs) to maintain tension over time remain poorly understood. Here, we demonstrate that confluent human umbilical vein endothelial cells (HUVECs) sustain stable traction forces for at least three days in the absence of external chemical or mechanical stimuli, indicating the presence of an intrinsic, active mechanism for long-term tension maintenance. Using fluorescent reporters and monolayer stress microscopy, we identify a Gq-G-protein-coupled receptor (GqGPCR) signaling pathway as a key regulator of this process. Imaging of an EC multicellular ensemble shows a collective phenomenon where DAG signaling consistently precedes increases in intracellular contractility, both at baseline and following histamine stimulation. Comparative analysis between ECs and airway smooth muscle cells (SMCs) showed that both cell types employ this conserved GqGPCR mediated “force-induced force generation” mechanism. Interestingly, SMCs exhibit fewer DAG signaling and contractility events than ECs over the same period, indicating greater efficiency in maintaining tension. Together, these findings demonstrate that endothelial cells actively regulate tension through continuous GqGPCR signaling where tension maintenance is a dynamic, collective process. This work provides new insight into how vascular tissues preserve mechanical homeostasis and suggests potential therapeutic targets for vascular endothelial dysfunction and age-related vascular stiffening.