About

Eno E. Ebong is an Associate Professor of Chemical Engineering and Bioengineering at Northeastern University, where he also serves as Associate Chair for Graduate Studies in Chemical Engineering. He directs the Ebong Mechanobiology Laboratory, focusing on studying how mechanical forces of blood flow and tissue stiffness influence endothelial cells that line blood vessels. His research aims to understand how mechanobiology affects the structure and function of the glycocalyx, a gel-like layer of sugar molecules and proteins coating endothelial cells, which plays a crucial role in protecting blood vessels from dysfunction and disease. His work involves constructing in vitro fluid-solid systems with endothelial and support cells, complemented by live animal studies, to uncover the mechanics-glycocalyx-endothelial cell relationship, with the goal of developing therapies and nanomedicine-based drug delivery tools to prevent or reverse vascular diseases. Dr. Ebong's educational background includes a B.S. in Mechanical Engineering from MIT, an M.Eng. and Ph.D. in Biomedical Engineering from Rensselaer Polytechnic Institute, and a postdoctoral fellowship at Albert Einstein College of Medicine and CUNY City College of New York. His research has been recognized with numerous awards, including the Presidential Early Career Award for Scientists and Engineers (PECASE) in 2025, and he is a Fellow of the American Institute for Medical and Biological Engineers.

Research topics

• Biology
• Medicine
• Internal medicine
• Cancer research
• Cell biology
• Pharmacology
• Immunology
• Chemistry
• Pathology
• Physics
• Mechanics
• Biochemistry
• Bioinformatics

Selected publications

• Sensing of shear stress in vascular endothelial cells – from physiology to pathology

  Journal of Cell Science · 2026-04-01

  article

  Sensing of mechanical force is crucial in regulating vascular homeostasis, physiology and disease. Endothelial cells line the lumens of blood vessels and are constantly exposed to flowing blood. This generates mechanical shear stress, which is instrumental in modulating endothelial cell behavior. Mechanosensitive proteins, including ion channels, G protein-coupled receptors (GPCR) and other cell surface receptors, adhesion molecules, integrins, primary cilia, cytoskeletal elements and the glycocalyx, transduce mechanical stimuli into biochemical signals that are essential for maintaining vascular integrity, responding to inflammatory stimuli and facilitating angiogenesis and arteriogenesis. Disruption in shear stress sensing can lead to pathological conditions, such as atherosclerosis or vascular anomalies. This Review article provides an integrated overview of the current knowledge on endothelial shear stress sensing and highlights key unanswered questions that will shape future research in vascular biology and disease.

  PublisherDOI

• Multimodal Profiling Reveals Distinct Endothelial Activation Pathways Regulated by Flow and Heparan Sulfate

  Cellular and Molecular Bioengineering · 2026-02-01

  articleOpen accessSenior author

  Abstract Purpose Atherosclerotic cardiovascular disease originates from endothelial dysfunction, characterized by a shift toward a pro-inflammatory state and increased production of reactive oxygen species (ROS). This dysfunction occurs under adverse mechanical conditions, such as blood flow oscillation, multi-directionality, recirculation, shear stress gradients, and low or stagnation flows. This study investigates how degradation of heparan sulfate (HS), a major component of the endothelial glycocalyx, drives the transition of endothelial cells from a functional, anti-inflammatory, and antioxidant phenotype under streamlined flow conditions to a dysfunctional, pro-inflammatory, and pro-oxidant phenotype when flow is stagnant. Pro-inflammatory and pro-oxidant endothelial behavior precedes atherosclerosis development. Methods Human aortic endothelial cells were exposed to uniform shear stress (14 dynes/cm 2 ) to model healthy endothelium. Unhealthy conditions were simulated via static conditions (0 dynes/cm 2 ) or enzymatic HS degradation using heparinase III. Endothelial cell phenotype was assessed using fluorescent labeling, confocal microscopy, Western blotting, and RNA sequencing. Results Endothelial cells conditioned by 14 dynes/cm 2 shear stress without heparinase III exhibited low expression of pro-inflammatory genes (HIF1A, VCAM1, and IL1B), minimal ROS production, and up-regulation of Kruppel-like transcription factors. Under the same flow conditions, HS degradation via heparinase III induced an inflammatory phenotype, resembling responses observed at 0 dynes/cm 2 shear stress, while ROS levels remained largely unaffected. Conclusions The endothelial glycocalyx is a protective, dynamic, and complex structure, with HS as a key component. This study demonstrates that intact HS mitigates endothelial dysfunction by suppressing inflammation linked to flow-dependent atherosclerosis, but not ROS production. Future research will focus on translating these findings into HS-targeted therapies for atherosclerotic cardiovascular disease.

  PublisherOA PDFDOI

• Co-therapy with S1P and heparan sulfate derivatives to restore endothelial glycocalyx and combat pro-atherosclerotic endothelial dysfunction

  Life Sciences · 2025-04-23 · 4 citations

  articleSenior authorCorresponding
  PublisherDOI

• Multimodal Magnetic Resonance Imaging with Mild Repetitive Head Injury in Awake Rats: Modeling the Human Experience and Clinical Condition

  Neuroscience Bulletin · 2025-06-29 · 2 citations

  articleOpen access

  Mild repetitive head injury is a serious health problem with long-term negative consequences. Changes in brain neurobiology were assessed with MRI in a model of head injury designed to reflect the human experience. Rats were maintained on a reverse light-dark cycle and head impacted daily at 24 h intervals over three days while fully awake under red light illumination. There was no neuroradiological evidence of brain damage. Rats were imaged for changes in blood brain barrier permeability, edema and gray matter microarchitecture, and resting state functional connectivity. Data were registered to a 3D MRI rat atlas with 173 segmented brain areas providing site-specific information on each imaging modality. Changes in BBB permeability were minimal and localized to the hippocampus and cerebellum. There was evidence of cytotoxic edema in the basal ganglia, thalamus, and cerebellum. There was a global decrease in connectivity and an increase in gliosis in the thalamus, cerebellum, and hippocampus. This study shows a sequelae of neuropathology caused by mild repetitive head injury that is commonly observed in clinical practice using MRI in patients. As such, it may serve as a model for testing the efficacy of new therapeutics using any or all of the measures as biomarkers to assess drug efficacy.

  PublisherOA PDFDOI

• Engineering Mechanical Microenvironments: Integration of Substrate and Flow Mechanics Reveals the Impact on the Endothelial Glycocalyx

  ACS Biomaterials Science & Engineering · 2025-05-28 · 2 citations

  articleOpen accessSenior authorCorresponding

  The glycocalyx (GCX), a multicomponent coating on endothelial cells (ECs), plays a critical role in various cellular behaviors, including barrier formation, vasodilation, and mechanotransduction. Mechanical perturbations in the vascular environment, such as blood vessel stiffness, are sensed and transduced by ECs via the GCX. Hypertension-induced stiffness disrupts GCX-mediated mechanotransduction, leading to EC dysfunction and atherosclerotic cardiovascular diseases. Understanding GCX-regulated mechanotransduction necessitates an in vitro model that closely mimics in vivo conditions. Existing models are insufficient, prompting the development of the system described in this manuscript. Here, we report on a new system to model varying EC substrate stiffness under sustained physiological fluid shear stress, providing a realistic environment for comprehensive examination of EC function. Gelatin methacrylate (GelMA) substrates with stiffnesses of 5 kPa (physiological) and 10 kPa (pathological) were seeded with human umbilical vein ECs (HUVECs) and subjected to constant physiological shear stress (12 dyn/cm2) for 6 h. Analysis focused on heparan sulfate (HS), sialic acid (SA), hyaluronic acid (HA), syndecan-1 (SDC1), cluster of differentiation 44 (CD44), and Yes-associated protein (YAP). Compared to the 5 kPa conditions, HS coverage and thickness decreased at 10 kPa, indicating impaired barrier function and increased susceptibility to inflammatory agents. SA density increased despite decreased coverage, suggesting enhanced binding site availability for inflammatory recruitment. HA expression remained unchanged, but the amount of the HA core receptor, CD44, was found to be increased at 10 kPa. Consistent with previously published interactions between CD44 and YAP, we observed increased YAP activation at 10 kPa, as evidenced by increased nuclear translocation and decreased phosphorylation. These findings, bridging biomaterials and mechanobiology approaches, deepen our understanding of how mechanical stimuli influence the EC GCX function. The results underscore the potential of mechanotherapeutic strategies aimed at preserving vascular health by modulating the endothelial function.

  PublisherDOI

• Lack of Laminar Shear Stress Facilitates the Endothelial Uptake of Very Small Superparamagnetic Iron Oxide Nanoparticles by Modulating the Endothelial Surface Layer

  International Journal of Nanomedicine · 2024-04-01 · 6 citations

  articleOpen access

  Purpose: To study whether the absence of laminar shear stress (LSS) enables the uptake of very small superparamagnetic iron oxide nanoparticles (VSOP) in endothelial cells by altering the composition, size, and barrier function of the endothelial surface layer (ESL). Methods and Results: A quantitative particle exclusion assay with living human umbilical endothelial cells using spinning disc confocal microscopy revealed that the dimension of the ESL was reduced in cells cultivated in the absence of LSS. By combining gene expression analysis, flow cytometry, high pressure freezing/freeze substitution immuno-transmission electron microscopy, and confocal laser scanning microscopy, we investigated changes in ESL composition. We found that increased expression of the hyaluronan receptor CD44 by absence of shear stress did not affect the uptake rate of VSOPs. We identified collagen as a previously neglected component of ESL that contributes to its barrier function. Experiments with inhibitor halofuginone and small interfering RNA (siRNA) demonstrated that suppression of collagen expression facilitates VSOP uptake in endothelial cells grown under LSS. Conclusion: The absence of laminar shear stress disturbs the barrier function of the ESL, facilitating membrane accessibility and endocytic uptake of VSOP. Collagen, a previously neglected component of ESL, contributes to its barrier function.

  PublisherOA PDFDOI

• Mechanisms of triple‐negative breast cancer extravasation: Impact of the physical environment and endothelial glycocalyx

  The FASEB Journal · 2024-07-01 · 3 citations

  articleOpen accessSenior authorCorresponding

  Cancer metastasis is the leading cause of death for those afflicted with cancer. In cancer metastasis, the cancer cells break off from the primary tumor, penetrate nearby blood vessels, and attach and extravasate out of the vessels to form secondary tumors at distant organs. This makes extravasation a critical step of the metastatic cascade. Herein, with a focus on triple-negative breast cancer, the role that the prospective secondary tumor microenvironment's mechanical properties play in circulating tumor cells' extravasation is reviewed. Specifically, the effects of the physically regulated vascular endothelial glycocalyx barrier element, vascular flow factors, and subendothelial extracellular matrix mechanical properties on cancer cell extravasation are examined. The ultimate goal of this review is to clarify the physical mechanisms that drive triple-negative breast cancer extravasation, as these mechanisms may be potential new targets for anti-metastasis therapy.

  PublisherOA PDFDOI

• Co-Therapy with S1P and Heparan Sulfate Derivatives to Restore Endothelial Glycocalyx and Combat Pro-Atherosclerotic Endothelial Dysfunction

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-11-08

  preprintOpen accessSenior authorCorresponding

  Endothelial cell (EC) glycocalyx (GCX) shedding due to disturbed blood flow and chemical factors leads to low-density lipoprotein infiltration and reduced nitric oxide synthesis, causing vascular dysfunction and atherosclerosis. This study evaluates a novel therapy combining sphingosine-1-phosphate (S1P) and heparin (heparan sulfate derivative). We hypothesized that heparin/S1P would repair mechanically damaged EC GCX in disturbed flow (DF) regions and restore anti-atherosclerotic mechanotransduction function, addressing cardiovascular disease. We used a parallel-plate flow chamber to simulate flow conditions in vitro and a partial carotid ligation mouse model to mimic DF in vivo. Heparin and albumin-bound S1P were administered to assess their reparative effects on the endothelial GCX. Immunocytochemistry, fluorescent staining, confocal microscopy, cellular alignment studies, and ultrasound were performed to evaluate EC function and endothelial-dependent vascular function. Barrier functionality was assessed via macrophage uptake. Heparin/S1P mechanism-of-action insights were gained through fluid dynamics simulations and staining of GCX synthesis enzyme as well as S1P receptor. Statistical analyses validated results. In vitro data showed that heparin/S1P therapy improves the function of DF-conditioned ECs by restoring EC GCX and promoting EC alignment and elevated vasodilator eNOS (endothelial-type nitric oxide synthase) expression. The in vivo studies confirmed GCX degradation, increased vessel inflammation and hyperpermeability, and vessel wall thickening in the partially ligated left carotid artery. Heparin/S1P treatment restored GCX in the left carotid artery, enhancing GCX thickness and coverage of the blood vessel wall. This work advances a new approach to regenerating the EC GCX and restoring its function in ECs under DF conditions.

  PublisherOA PDFDOI

• Unraveling neurovascular mysteries: the role of endothelial glycocalyx dysfunction in Alzheimer’s disease pathogenesis

  Frontiers in Physiology · 2024-07-04 · 5 citations

  reviewOpen accessSenior authorCorresponding

  While cardiovascular disease, cancer, and human immunodeficiency virus (HIV) mortality rates have decreased over the past 20 years, Alzheimer's Disease (AD) deaths have risen by 145% since 2010. Despite significant research efforts, effective AD treatments remain elusive due to a poorly defined etiology and difficulty in targeting events that occur too downstream of disease onset. In hopes of elucidating alternative treatment pathways, now, AD is commonly being more broadly defined not only as a neurological disorder but also as a progression of a variety of cerebrovascular pathologies highlighted by the breakdown of the blood-brain barrier. The endothelial glycocalyx (GCX), which is an essential regulator of vascular physiology, plays a crucial role in the function of the neurovascular system, acting as an essential vascular mechanotransducer to facilitate ultimate blood-brain homeostasis. Shedding of the cerebrovascular GCX could be an early indication of neurovascular dysfunction and may subsequently progress neurodegenerative diseases like AD. Recent advances in in vitro modeling, gene/protein silencing, and imaging techniques offer new avenues of scrutinizing the GCX's effects on AD-related neurovascular pathology. Initial studies indicate GCX degradation in AD and other neurodegenerative diseases and have begun to demonstrate a possible link to GCX loss and cerebrovascular dysfunction. This review will scrutinize the GCX's contribution to known vascular etiologies of AD and propose future work aimed at continuing to uncover the relationship between GCX dysfunction and eventual AD-associated neurological deterioration.

  PublisherOA PDFDOI

• <em>In Vitro</em> Model Integrating Substrate Stiffness and Flow to Study Endothelial Cell Responses

  Journal of Visualized Experiments · 2024-07-19 · 1 citations

  articleSenior author

  We present an innovative in vitro model aimed at investigating the combined effects of tissue rigidity and shear stress on endothelial cell (EC) function, which are crucial for understanding vascular health and the onset of diseases such as atherosclerosis. Traditionally, studies have explored the impacts of shear stress and substrate stiffness on ECs, independently. However, this integrated system combines these factors to provide a more precise simulation of the mechanical environment of the vasculature. The objective is to examine EC mechanotransduction across various tissue stiffness levels and flow conditions using human ECs. We detail the protocol for synthesizing gelatin methacrylate (GelMA) hydrogels with tunable stiffness and seeding them with ECs to achieve confluency. Additionally, we describe the design and assembly of a cost-effective flow chamber, supplemented by computational fluid dynamics simulations, to generate physiological flow conditions characterized by laminar flow and appropriate shear stress levels. The protocol also incorporates fluorescence labeling for confocal microscopy, enabling the assessment of EC responses to both tissue compliance and flow conditions. By subjecting cultured ECs to multiple integrated mechanical stimuli, this model enables comprehensive investigations into how factors such as hypertension and aging may affect EC function and EC-mediated vascular diseases. The insights gained from these investigations will be instrumental in elucidating the mechanisms underlying vascular diseases and in developing effective treatment strategies.

  PublisherDOI

Recent grants

• Atheroprotective vs. Atherogenic Glycocalyx Mechanotransduction Mechanisms

  NIH · $770k · 2015–2020

• CAREER: EMBRACE STEM (Endothelial MechanoBiology Research And multiCultural Education in STEM)

  NSF · $608k · 2019–2025

Frequent coauthors

• Ian C. Harding

  Wave Life Sciences (United States)

  140 shared

• Danielle Kamato

  Griffith University

  121 shared

• Sihui Luo

  Hefei University

  121 shared

• Iqra Ilyas

  University of Science and Technology of China

  121 shared

• Zhuoming Li

  Sun Yat-sen University

  121 shared

• Peiqing Liu

  Sun Yat-sen University

  121 shared

• Xueying Zheng

  Fudan University

  121 shared

• Suowen Xu

  Max Planck Institute for Heart and Lung Research

  121 shared

Labs

• Ebong Mechanobiology LaboratoryPI

Awards & honors

• Presidential Early Career Award for Scientists and Engineers…
• American Institute for Medical and Biological Engineers Fell…
• Diversity Recognition Award (2024)
• NIH Mentored Research Scientist Career Development Award (20…
• NSF Faculty Early Career Development Program (CAREER) Award…